Top

Published in:

Open Access 01-04-2017 | Review Article

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

Authors: Mateusz Florczuk, Adam Szpechcinski, Joanna Chorostowska-Wynimko

Published in: Targeted Oncology | Issue 2/2017

Abstract

Lung cancer is the most common cancer worldwide. Up to 85% of lung cancer cases are diagnosed as non-small cell lung cancer (NSCLC). The effectiveness of NSCLC treatment is expected to be improved through the implementation of robust and specific biomarkers. MicroRNAs (miRNAs) are small, non-coding molecules that play a key role in the regulation of basic cellular processes, including differentiation, proliferation and apoptosis, by controlling gene expression at the post-transcriptional level. Deregulation of miRNA activity results in the loss of homeostasis and the development of a number of pathologies, including lung cancer. During lung carcinogenesis, miRNAs exhibit dual regulatory function: they act as oncogenes to promote cancer development or as tumour suppressors. Unique miRNA sequences have been detected in malignant tissues and corresponding healthy tissues. Furthermore, stable forms of tumour-related miRNAs are detectable in the peripheral blood of patients with NSCLC. The potential benefits of using extracellular miRNAs present in body fluids as part of the diagnostic evaluation of cancer include low invasiveness (compared with tumour cell/tissue sampling), and the repeatability and ease of obtaining the specimens. Apart from the diagnostic applications of altered miRNA expression profiles, the dual regulatory role of miRNA in cancer might drive the further development of personalised therapies in NSCLC. The clinical usefulness of miRNA expression analysis to predict the efficacy of various treatment strategies including surgery, radio- and chemotherapy, and targeted therapies has been evaluated in NSCLC. Also, the capacity of a single miRNA to regulate the expression of multiple genes simultaneously presents an opportunity to use these small molecules in personalised therapy as individualised therapeutic tools.

Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol. 2016;893:1–19. doi:10.1007/978-3-319-24223-1_1.PubMedCrossRef

Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review 1975–2013. In: National Cancer Institute. 2015. http://seer.cancer.gov/csr/1975_2013/. Accessed Based on November 2015 SEER data submission, posted to the SEER web site, April 2016 accessed: 2.01.2016.

Fabbri M. MicroRNAs and cancer: towards a personalized medicine. Curr Mol Med. 2013;13(5):751–6.PubMedCrossRef

Saumet A, Mathelier A, Lecellier CH. The potential of microRNAs in personalized medicine against cancers. Biomed Res Int. 2014;2014:642916. doi:10.1155/2014/642916.PubMedPubMedCentralCrossRef

National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395–409. doi:10.1056/NEJMoa1102873.CrossRef

Sozzi G, Boeri M, Rossi M, et al. Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: a correlative MILD Trial Study. J Clin Oncol. 2014;32(8):768–73. doi:10.1200/JCO.2013.50.4357.PubMedPubMedCentralCrossRef

Montani F, Marzi MJ, Dezi F, et al. miR-Test: a blood test for lung cancer early detection. J Natl Cancer Inst. 2015;107(6):djv063. doi:10.1093/jnci/djv063.PubMedCrossRef

Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Translat Lung Cancer Res. 2015;4(1):36–54. doi:10.3978/j.issn.2218-6751.2014.05.01.

Sin TK, Wang F, Meng F, et al. Implications of MicroRNAs in the treatment of gefitinib-resistant non-small cell lung cancer. Int J Mol Sci. 2016;17(2):237. doi:10.3390/ijms17020237.

10.

Schvartsman G, Ferrarotto R, Massarelli E. Checkpoint inhibitors in lung cancer: latest developments and clinical potential. Ther Adv Med Oncol. 2016;8(6):460–73. doi:10.1177/1758834016661164.PubMedPubMedCentralCrossRef

11.

Paladini L, Fabris L, Bottai G, Raschioni C, Calin GA, Santarpia L. Targeting microRNAs as key modulators of tumor immune response. J Exp Clin Cancer Res. 2016;35(1):103. doi:10.1186/s13046-016-0375-2.PubMedPubMedCentralCrossRef

12.

Gebert LFR, Rebhan MAE, Crivelli SEM, Denzler R, Stoffel M, Hall J. Miravirsen (SPC3649) can inhibit the biogenesis of miR-122. Nucleic Acids Research. 2014;42(1):609-621. doi:10.1093/nar/gkt852.

13.

Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature. 2008;455(7209):64–71. doi:10.1038/nature07242.PubMedPubMedCentralCrossRef

14.

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.PubMedCrossRef

15.

Turchinovich A, Weiz L, Burwinkel B. Extracellular miRNAs: the mystery of their origin and function. Trends Biochem Sci. 2012;37(11):460–5. doi:10.1016/j.tibs.2012.08.003.PubMedCrossRef

16.

Chou CH, Chang NW, Shrestha S, et al. miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res. 2016;44(D1):D239–47. doi:10.1093/nar/gkv1258.CrossRefPubMed

17.

Chang S, Johnston Jr RJ, Frokjaer-Jensen C, Lockery S, Hobert O. MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode. Nature. 2004;430(7001):785–9. doi:10.1038/nature02752.PubMedCrossRef

18.

Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP. Vertebrate microRNA genes. Science. 2003;299(5612):1540. doi:10.1126/science.1080372.PubMedCrossRef

19.

Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005;120(1):21–4. doi:10.1016/j.cell.2004.12.031.PubMedCrossRef

20.

Giovannetti E, Erozenci A, Smit J, Danesi R, Peters GJ. Molecular mechanisms underlying the role of microRNAs (miRNAs) in anticancer drug resistance and implications for clinical practice. Crit Rev Oncol Hematol. 2012;81(2):103–22. doi:10.1016/j.critrevonc.2011.03.010.

21.

Macfarlane LA, Murphy PR. MicroRNA: biogenesis, function and role in cancer. Curr Genomics. 2010;11(7):537–61. doi:10.2174/138920210793175895.PubMedPubMedCentralCrossRef

22.

Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R. MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A. 2008;105(5):1608–13. doi:10.1073/pnas.0707594105.

23.

Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, Plasterk RH. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 2001;15(20):2654–9. doi:10.1101/gad.927801.PubMedPubMedCentralCrossRef

24.

Sun T, Kalionis B, Lv G, Xia S, Gao W. Role of exosomal noncoding RNAs in lung carcinogenesis. Biomed Res Int. 2015;2015:125807. doi:10.1155/2015/125807.PubMedPubMedCentral

25.

Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425(6956):415–9. doi:10.1038/nature01957.PubMedCrossRef

26.

Basyuk E, Suavet F, Doglio A, Bordonne R, Bertrand E. Human let-7 stem-loop precursors harbor features of RNase III cleavage products. Nucleic Acids Res. 2003;31(22):6593–7.PubMedPubMedCentralCrossRef

27.

Zeng Y, Cullen BR. Sequence requirements for micro RNA processing and function in human cells. RNA. 2003;9(1):112–23.PubMedPubMedCentralCrossRef

28.

Cullen BR. Transcription and processing of human microRNA precursors. Mol Cell. 2004;16(6):861–5. doi:10.1016/j.molcel.2004.12.002.PubMedCrossRef

29.

Gregory RI, Yan KP, Amuthan G, et al. The microprocessor complex mediates the genesis of microRNAs. Nature. 2004;432(7014):235–40. doi:10.1038/nature03120.PubMedCrossRef

30.

Lee YS, Nakahara K, Pham JW, et al. Distinct roles for drosophila dicer-1 and dicer-2 in the siRNA/miRNA silencing pathways. Cell. 2004;117(1):69–81.PubMedCrossRef

31.

Cai XZ, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA. 2004;10(12):1957–66. doi:10.1261/rna.7135204.PubMedPubMedCentralCrossRef

32.

Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary microRNAs by the microprocessor complex. Nature. 2004;432(7014):231–5. doi:10.1038/nature03049.PubMedCrossRef

33.

Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17(24):3011–6. doi:10.1101/gad.1158803.PubMedPubMedCentralCrossRef

34.

Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001;293(5531):834–8. doi:10.1126/science.1062961.PubMedCrossRef

35.

Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA. 2004;10(2):185–91. doi:10.1261/rna.5167604.PubMedPubMedCentralCrossRef

36.

Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002;21(17):4663–70.PubMedPubMedCentralCrossRef

37.

Isik M, Korswagen HC, Berezikov E. Expression patterns of intronic microRNAs in Caenorhabditis elegans. Silence. 2010;1(1):5. doi:10.1186/1758-907X-1-5.PubMedPubMedCentralCrossRef

38.

Lee Y, Kim M, Han J, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23(20):4051–60. doi:10.1038/sj.emboj.7600385.PubMedPubMedCentralCrossRef

39.

Shomron N, Levy C. MicroRNA-biogenesis and Pre-mRNA splicing crosstalk. J Biomed Biotechnol. 2009;2009:594678. doi:10.1155/2009/594678.PubMedPubMedCentral

40.

Liu C, Zhang F, Li T, et al. MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs. BMC Genomics. 2012;13:661. doi:10.1186/1471-2164-13-661.PubMedPubMedCentralCrossRef

41.

de la Chapelle A, Jazdzewski K. MicroRNAs in thyroid cancer. J Clin Endocrinol Metab. 2011;96(11):3326–36. doi:10.1210/jc.2011-1004.PubMedPubMedCentralCrossRef

42.

Hu Z, Chen J, Tian T, et al. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest. 2008;118(7):2600–8. doi:10.1172/JCI34934.PubMedPubMedCentral

43.

Tian T, Shu Y, Chen J, et al. A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomark Prev. 2009;18(4):1183–7. doi:10.1158/1055-9965.EPI-08-0814.CrossRef

44.

Yuan Z, Zeng X, Yang D, Wang W, Liu Z. Effects of common polymorphism rs11614913 in Hsa-miR-196a2 on lung cancer risk. PLoS One. 2013;8(4):e61047. doi:10.1371/journal.pone.0061047.PubMedPubMedCentralCrossRef

45.

Czubak K, Lewandowska MA, Klonowska K, et al. High copy number variation of cancer-related microRNA genes and frequent amplification of DICER1 and DROSHA in lung cancer. Oncotarget. 2015;6(27):23399–416. doi:10.18632/oncotarget.4351.PubMedPubMedCentralCrossRef

46.

Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10(10):704–14. doi:10.1038/nrg2634.PubMedPubMedCentralCrossRef

47.

Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103(7):2257–61. doi:10.1073/pnas.0510565103.PubMedPubMedCentralCrossRef

48.

Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8. doi:10.1038/nature03702.PubMedCrossRef

49.

Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006. doi:10.1038/cr.2008.282.PubMedCrossRef

50.

Gilad S, Meiri E, Yogev Y, et al. Serum microRNAs are promising novel biomarkers. PLoS One. 2008;3(9):e3148. doi:10.1371/journal.pone.0003148.PubMedPubMedCentralCrossRef

51.

Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513–8. doi:10.1073/pnas.0804549105.PubMedPubMedCentralCrossRef

52.

Park NJ, Zhou H, Elashoff D, et al. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res. 2009;15(17):5473–7. doi:10.1158/1078-0432.CCR-09-0736.PubMedPubMedCentralCrossRef

53.

Hanke M, Hoefig K, Merz H, et al. A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol Semin Ori. 2010;28(6):655–61. doi:10.1016/j.urolonc.2009.01.027.CrossRef

54.

Kosaka N, Izumi H, Sekine K, Ochiya T. microRNA as a new immune-regulatory agent in breast milk. Silence. 2010;1:7.PubMedPubMedCentralCrossRef

55.

Cogswell JP, Ward J, Taylor IA, et al. Identification of miRNA changes in Alzheimer’s disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis. 2008;14(1):27–41.PubMed

56.

Hanson EK, Lubenow H, Ballantyne J. Identification of forensically relevant body fluids using a panel of differentially expressed microRNAs. Anal Biochem. 2009;387(2):303–14. doi:10.1016/j.ab.2009.01.037.PubMedCrossRef

57.

Rodriguez M, Silva J, Lopez-Alfonso A, et al. Different exosome cargo from plasma/bronchoalveolar lavage in non-small-cell lung cancer. Genes Chromosom Cancer. 2014;53(9):713–24. doi:10.1002/gcc.22181.PubMed

58.

Molina-Pinelo S, Pastor MD, Suarez R, et al. MicroRNA clusters: dysregulation in lung adenocarcinoma and COPD. Eur Respir J. 2014;43(6):1740–9. doi:10.1183/09031936.00091513.PubMedCrossRef

59.

Wang T, Lv M, Shen S, et al. Cell-free microRNA expression profiles in malignant effusion associated with patient survival in non-small cell lung cancer. PLoS One. 2012;7(8):e43268. doi:10.1371/journal.pone.0043268.PubMedPubMedCentralCrossRef

60.

Xie L, Chen X, Wang L, et al. Cell-free miRNAs may indicate diagnosis and docetaxel sensitivity of tumor cells in malignant effusions. BMC Cancer. 2010;10:591. doi:10.1186/1471-2407-10-591.PubMedPubMedCentralCrossRef

61.

Zen K, Zhang CY. Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev. 2012;32(2):326–48. doi:10.1002/med.20215.PubMedCrossRef

62.

Schwarzenbach H, Nishida N, Calin GA, Pantel K. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 2014;11(3):145–56. doi:10.1038/nrclinonc.2014.5.PubMedCrossRef

63.

Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011;39(16):7223–33. doi:10.1093/nar/gkr254.PubMedPubMedCentralCrossRef

64.

Weber JA, Baxter DH, Zhang S, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733–41. doi:10.1373/clinchem.2010.147405.PubMedPubMedCentralCrossRef

65.

Akat KM, Moore-McGriff D, Morozov P, et al. Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers. Proc Natl Acad Sci U S A. 2014;111(30):11151–6. doi:10.1073/pnas.1401724111.PubMedPubMedCentralCrossRef

66.

Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med. 2014;20(8):460–9. doi:10.1016/j.molmed.2014.06.005.PubMedCrossRef

67.

Rabinowits G, Gercel-Taylor C, Day JM, Taylor DD, Kloecker GH. Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer. 2009;10(1):42–6. doi:10.3816/CLC.2009.n.006.PubMedCrossRef

68.

Hannafon BN, Ding W-Q. Intercellular communication by exosome-derived microRNAs in cancer. Int J Mol Sci. 2013;14(7):14240–69. doi:10.3390/ijms140714240.PubMedPubMedCentralCrossRef

69.

Frydrychowicz M, Kolecka-Bednarczyk A, Madejczyk M, Yasar S, Dworacki G. Exosomes - structure, biogenesis and biological role in non-small-cell lung cancer. Scand J Immunol. 2015;81(1):2–10. doi:10.1111/sji.12247.PubMedCrossRef

70.

Ardekani AM, Naeini MM. The role of MicroRNAs in human diseases. Avicenna J Med Biotechnol. 2010;2(4):161–79.PubMedPubMedCentral

71.

Esposito A, Criscitiello C, Locatelli M, Milano M, Curigliano G. Liquid biopsies for solid tumors: understanding tumor heterogeneity and real time monitoring of early resistance to targeted therapies. Pharmacol Ther. 2016;157:120–4. doi:10.1016/j.pharmthera.2015.11.007.PubMedCrossRef

72.

Zandberga E, Kozirovskis V, Abols A, Andrejeva D, Purkalne G, Line A. Cell-free microRNAs as diagnostic, prognostic, and predictive biomarkers for lung cancer. Genes Chromosom Cancer. 2013;52(4):356–69. doi:10.1002/gcc.22032.PubMedCrossRef

73.

Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010;50(4):298–301. doi:10.1016/j.ymeth.2010.01.032.PubMedPubMedCentralCrossRef

74.

Zampetaki A, Mayr M. Analytical challenges and technical limitations in assessing circulating MiRNAs. Thromb Haemost. 2012;108(10):592–8. doi:10.1160/TH12-02-0097.PubMedCrossRef

75.

Schwarzenbach H, da Silva AM, Calin G, Pantel K. Data normalization strategies for MicroRNA quantification. Clin Chem. 2015;61(11):1333–42. doi:10.1373/clinchem.2015.239459.PubMedPubMedCentralCrossRef

76.

Tiberio P, Callari M, Angeloni V, Daidone MG, Appierto V. Challenges in using circulating miRNAs as cancer biomarkers. Biomed Res Int. 2015;2015:10.CrossRef

77.

Ferdin J, Kunej T, Calin GA. Non-coding RNAs: identification of cancer-associated microRNAs by gene profiling. Technol Cancer Res Treat. 2010;9(2):123–38.PubMedCrossRef

78.

Calin GA, Sevignani C, Dumitru CD, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101(9):2999–3004. doi:10.1073/pnas.0307323101.PubMedPubMedCentralCrossRef

79.

Zhang BH, Pan XP, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302(1):1–12. doi:10.1016/j.ydbio.2006.08.028.PubMedCrossRef

80.

Hirsch FR, Franklin WA, Gazdar AF, Bunn Jr PA. Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology. Clin Cancer Res. 2001;7(1):5–22.PubMed

81.

Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69. doi:10.1038/nrc1840.PubMedCrossRef

82.

Yu SL, Chen HY, Chang GC, et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 2008;13(1):48–57. doi:10.1016/j.ccr.2007.12.008.PubMedCrossRef

83.

Dvinge H, Git A, Graf S, et al. The shaping and functional consequences of the microRNA landscape in breast cancer. Nature. 2013;497(7449):378–82. doi:10.1038/nature12108.PubMedCrossRef

84.

Nasser MW, Datta J, Nuovo G, et al. Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J Biol Chem. 2008;283(48):33394–405. doi:10.1074/jbc.M804788200.PubMedPubMedCentralCrossRef

85.

Garofalo M, Quintavalle C, Di Leva G, et al. MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene. 2008;27(27):3845–55. doi:10.1038/onc.2008.6.PubMedCrossRef

86.

Hayashita Y, Osada H, Tatematsu Y, et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 2005;65(21):9628–32. doi:10.1158/0008-5472.CAN-05-2352.PubMedCrossRef

87.

He W-J, Li W-H, Jiang B, Wang Y-F, Xia Y-X, Wang L. MicroRNAs level as an initial screening method for early-stage lung cancer: a bivariate diagnostic random-effects meta-analysis. Int J Clin Exp Med. 2015;8(8):12317–26.PubMedPubMedCentral

88.

Wang H, Wu S, Zhao L, Zhao J, Liu J, Wang Z. Clinical use of microRNAs as potential non-invasive biomarkers for detecting non-small cell lung cancer: a meta-analysis. Respirology. 2015;20(1):56–65. doi:10.1111/resp.12444.PubMedCrossRef

89.

Boeri M, Verri C, Conte D, et al. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci U S A. 2011;108(9):3713–8. doi:10.1073/pnas.1100048108.PubMedPubMedCentralCrossRef

90.

Hennessey PT, Sanford T, Choudhary A, et al. Serum microRNA biomarkers for detection of non-small cell lung cancer. PLoS One. 2012;7(2):e32307. doi:10.1371/journal.pone.0032307.PubMedPubMedCentralCrossRef

91.

Solomides CC, Evans BJ, Navenot JM, Vadigepalli R, Peiper SC, Wang ZX. MicroRNA profiling in lung cancer reveals new molecular markers for diagnosis. Acta Cytol. 2012;56(6):645–54. doi:10.1159/000343473.PubMedCrossRef

92.

Cazzoli R, Buttitta F, Di Nicola M, Malatesta S, Marchetti A, Pass HI. MicroRNAs derived from circulating exosomes as non-invasive biomarkers for screening and diagnose lung cancer. J Thorac Oncol. 2013;8(9):1156–62. doi:10.1097/JTO.0b013e318299ac32.PubMedPubMedCentralCrossRef

93.

Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Translat Lung Cancer Res. 2014;3(4):242–9. doi:10.3978/j.issn.2218-6751.2013.12.05.

94.

Boyd JA, Hubbs JL, Kim DW, Hollis D, Marks LB, Kelsey CR. Timing of local and distant failure in resected lung cancer: implications for reported rates of local failure. J Thorac Oncol. 2010;5(2):211–4. doi:10.1097/JTO.0b013e3181c20080.PubMedCrossRef

95.

Leidinger P, Keller A, Backes C, Huwer H, Meese E. MicroRNA expression changes after lung cancer resection: a follow-up study. RNA Biol. 2012;9(6):900–10. doi:10.4161/rna.20107.PubMedCrossRef

96.

Leidinger P, Galata V, Backes C, et al. Longitudinal study on circulating miRNAs in patients after lung cancer resection. Oncotarget. 2015;6(18):16674–85. doi:10.18632/oncotarget.4322.PubMedPubMedCentralCrossRef

97.

Li W, Wang Y, Zhang Q, et al. MicroRNA-486 as a biomarker for early diagnosis and recurrence of non-small cell lung cancer. PLoS One. 2015;10(8):e0134220. doi:10.1371/journal.pone.0134220.PubMedPubMedCentralCrossRef

98.

Hu Z, Chen X, Zhao Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 2010;28(10):1721–6. doi:10.1200/JCO.2009.24.9342.PubMedCrossRef

99.

Le HB, Zhu WY, Chen DD, et al. Evaluation of dynamic change of serum miR-21 and miR-24 in pre- and post-operative lung carcinoma patients. Med Oncol. 2012;29(5):3190–7. doi:10.1007/s12032-012-0303-z.PubMedCrossRef

100.

Cellini F, Morganti AG, Genovesi D, Silvestris N, Valentini V. Role of microRNA in response to ionizing radiations: evidences and potential impact on clinical practice for radiotherapy. Molecules. 2014;19(4):5379–401. doi:10.3390/molecules19045379.PubMedCrossRef

101.

Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11(4):239–53. doi:10.1038/nrc3007.PubMedCrossRef

102.

Weidhaas JB, Babar I, Nallur SM, et al. MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Res. 2007;67(23):11111–6.PubMedCrossRef

103.

Lee KM, Choi EJ, Kim IA. microRNA-7 increases radiosensitivity of human cancer cells with activated EGFR-associated signaling. Radiother Oncol. 2011;101(1):171–6. doi:10.1016/j.radonc.2011.05.050.PubMedCrossRef

104.

Duan W, Xu Y, Dong Y, Cao L, Tong J, Zhou X. Ectopic expression of miR-34a enhances radiosensitivity of non-small cell lung cancer cells, partly by suppressing the LyGDI signaling pathway. J Radiat Res. 2013;54(4):611–9. doi:10.1093/jrr/rrs136.PubMedPubMedCentralCrossRef

105.

Cortez MA, Valdecanas D, Niknam S, et al. In vivo delivery of miR-34a sensitizes lung tumors to radiation through RAD51 regulation. Mol Ther Nucleic Acids. 2015;4:e270. doi:10.1038/mtna.2015.47.PubMedPubMedCentralCrossRef

106.

Salim H, Akbar NS, Zong D, et al. miRNA-214 modulates radiotherapy response of non-small cell lung cancer cells through regulation of p38MAPK, apoptosis and senescence. Br J Cancer. 2012;107(8):1361–73. doi:10.1038/bjc.2012.382.PubMedPubMedCentralCrossRef

107.

Ma W, Ma CN, Zhou NN, Li XD, Zhang YJ. Up-regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy. Sci Rep. 2016;6:31651. doi:10.1038/srep31651.PubMedPubMedCentralCrossRef

108.

Tian F, Han Y, Yan X, et al. Upregulation of microrna-451 increases the sensitivity of A549 cells to radiotherapy through enhancement of apoptosis. Thorac Cancer. 2016;7(2):226–31. doi:10.1111/1759-7714.12318.PubMedCrossRef

109.

Liu YJ, Lin YF, Chen YF, Luo EC, Sher YP, et al. (2013) MicroRNA-449a Enhances Radiosensitivity in CL1-0 Lung Adenocarcinoma Cells. PLOS ONE 8(4): e62383. doi: 10.1371/journal.pone.0062383.

110.

Wang XC, Du LQ, Tian LL, et al. Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer. Lung Cancer. 2011;72(1):92–9. doi:10.1016/j.lungcan.2010.07.014.

111.

Bi N, Schipper M, Stanton P, Wang W, Kong F-M. Serum miRNA signature to identify a patient’s resistance to high-dose radiation therapy for unresectable non-small cell lung cancer. J Clin Oncol. 2013;31(Suppl:abstr 7580).

112.

Chen X, Xu Y, Liao X, et al. Plasma miRNAs in predicting radiosensitivity in non-small cell lung cancer. Tumour Biol. 2016;37(9):11927–36. doi:10.1007/s13277-016-5052-8.PubMedPubMedCentralCrossRef

113.

Ponomaryova AA, Morozkin ES, Rykova EY, et al. Dynamic changes in circulating miRNA levels in response to antitumor therapy of lung cancer. Exp Lung Res. 2016;42(2):95–102. doi:10.3109/01902148.2016.1155245.PubMedCrossRef

114.

Cui E-H, Li H-J, Hua F, et al. Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC patients receiving cisplatin-based chemotherapy. Acta Pharmacol Sin. 2013;34(2):309–13. doi:10.1038/aps.2012.125.PubMedCrossRef

115.

Gao W, Lu X, Liu L, Xu J, Feng D, Shu Y. MiRNA-21: a biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer. Cancer Biol Ther. 2012;13(5):330–40. doi:10.4161/cbt.19073.PubMedCrossRef

116.

Zhang X, Zhu J, Xing R, et al. miR-513a-3p sensitizes human lung adenocarcinoma cells to chemotherapy by targeting GSTP1. Lung Cancer. 2012;77(3):488–94. doi:10.1016/j.lungcan.2012.05.107.PubMedCrossRef

117.

Ishii T, Fujishiro M, Masuda M, Teramoto S, Matsuse T. A methylated oligonucleotide induced methylation of GSTP1 promoter and suppressed its expression in A549 lung adenocarcinoma cells. Cancer Lett. 2004;212(2):211–23. doi:10.1016/j.canlet.2004.03.001.PubMedCrossRef

118.

Wang J, Zhang J, Zhang L, et al. Expression of P-gp, MRP, LRP, GST-pi and TopoIIalpha and intrinsic resistance in human lung cancer cell lines. Oncol Rep. 2011;26(5):1081–9. doi:10.3892/or.2011.1405.PubMed

119.

Rui W, Bing F, Hai-Zhu S, Wei D, Long-Bang C. Identification of microRNA profiles in docetaxel-resistant human non-small cell lung carcinoma cells (SPC-A1). J Cell Mol Med. 2010;14(1–2):206–14. doi:10.1111/j.1582-4934.2009.00964.x.PubMedCrossRef

120.

Feng B, Wang R, Song HZ, Chen LB. MicroRNA-200b reverses chemoresistance of docetaxel-resistant human lung adenocarcinoma cells by targeting E2F3. Cancer. 2012;118(13):3365–76. doi:10.1002/cncr.26560.PubMedCrossRef

121.

Feng B, Wang R, Chen LB. MiR-100 resensitizes docetaxel-resistant human lung adenocarcinoma cells (SPC-A1) to docetaxel by targeting Plk1. Cancer Lett. 2012;317(2):184–91. doi:10.1016/j.canlet.2011.11.024.PubMedCrossRef

122.

Cui SY, Huang JY, Chen YT, et al. Let-7c governs the acquisition of chemo- or radioresistance and epithelial-to-mesenchymal transition phenotypes in docetaxel-resistant lung adenocarcinoma. Mol Cancer Res. 2013;11(7):699–713. doi:10.1158/1541-7786.MCR-13-0019-T.PubMedCrossRef

123.

Zhang JG, Guo JF, Liu DL, Liu Q, Wang JJ. MicroRNA-101 exerts tumor-suppressive functions in non-small cell lung cancer through directly targeting enhancer of zeste homolog 2. J Thorac Oncol. 2011;6(4):671–8. doi:10.1097/JTO.0b013e318208eb35.PubMedCrossRef

124.

Chatterjee A, Chattopadhyay D, Chakrabarti G. MiR-16 targets Bcl-2 in paclitaxel-resistant lung cancer cells and overexpression of miR-16 along with miR-17 causes unprecedented sensitivity by simultaneously modulating autophagy and apoptosis. Cell Signal. 2015;27(2):189–203. doi:10.1016/j.cellsig.2014.11.023.PubMedCrossRef

125.

Chatterjee A, Chattopadhyay D, Chakrabarti G. miR-17-5p downregulation contributes to paclitaxel resistance of lung cancer cells through altering beclin1 expression. PLoS One. 2014;9(4):e95716. doi:10.1371/journal.pone.0095716.PubMedPubMedCentralCrossRef

126.

Holleman A, Chung I, Olsen RR, et al. miR-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo. Oncogene. 2011;30(43):4386–98. doi:10.1038/onc.2011.148.PubMedPubMedCentralCrossRef

127.

Shen H, Wang L, Ge X, Jiang CF, et al. MicroRNA-137 inhibits tumor growth and sensitizes chemosensitivity to paclitaxel and cisplatin in lung cancer. Oncotarget. 2016;7(15):20728–42. doi:10.18632/oncotarget.8011.

128.

Ye J, Zhang Z, Sun L, Fang Y, Xu X, Zhou G. miR-186 regulates chemo-sensitivity to paclitaxel via targeting MAPT in non-small cell lung cancer (NSCLC). Mol BioSyst. 2016;12(11):3417–24. doi:10.1039/c6mb00576d.PubMedCrossRef

129.

Ahmadzadeh M, Johnson LA, Heemskerk B, et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009;114(8):1537–44. doi:10.1182/blood-2008-12-195792.PubMedPubMedCentralCrossRef

130.

Brahmer JR, Pardoll DM. Immune checkpoint inhibitors: making immunotherapy a reality for the treatment of lung cancer. Cancer Immunol Res. 2013;1(2):85–91. doi:10.1158/2326-6066.CIR-13-0078.PubMedPubMedCentralCrossRef

131.

Chen L, Gibbons DL, Goswami S, et al. Metastasis is regulated via microRNA-200/ZEB1 axis control of tumor cell PD-L1 expression and intratumoral immunosuppression. Nat Commun. 2014;5:5241. doi:10.1038/ncomms6241.PubMedPubMedCentralCrossRef

132.

Gibbons DL, Lin W, Creighton CJ, et al. Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes Dev. 2009;23(18):2140–51. doi:10.1101/gad.1820209.PubMedPubMedCentralCrossRef

133.

Gibbons DL, Lin W, Creighton CJ, et al. Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma. PLoS One. 2009;4(4):e5401. doi:10.1371/journal.pone.0005401.PubMedPubMedCentralCrossRef

134.

Cortez MA, Ivan C, Valdecanas D, et al. PDL1 Regulation by p53 via miR-34. J Natl Cancer Inst. 2016;108(1):djv303.PubMedCrossRef

135.

Garofalo M, Jeon Y-J, Nuovo GJ, et al. MiR-34a/c-dependent PDGFR-α/β downregulation inhibits tumorigenesis and enhances TRAIL-induced apoptosis in lung cancer. PLoS One. 2013;8(6):e67581. doi:10.1371/journal.pone.0067581.PubMedPubMedCentralCrossRef

136.

Xie Y, Tobin LA, Camps J, et al. MicroRNA-24 regulates XIAP to reduce the apoptosis threshold in cancer cells. Oncogene. 2013;32(19):2442–51. doi:10.1038/onc.2012.258.PubMedCrossRef

137.

Joshi P, Jeon YJ, Lagana A, et al. MicroRNA-148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC. Proc Natl Acad Sci U S A. 2015;112(28):8650–5. doi:10.1073/pnas.1500886112.PubMedPubMedCentralCrossRef

138.

Jeon YJ, Middleton J, Kim T, et al. A set of NF-kappaB-regulated microRNAs induces acquired TRAIL resistance in lung cancer. Proc Natl Acad Sci U S A. 2015;112(26):E3355–64. doi:10.1073/pnas.1504630112.PubMedPubMedCentralCrossRef

139.

Chorostowska-Wynimko J, Szpechcinski A. The impact of genetic markers on the diagnosis of lung cancer: a current perspective. J Thorac Oncol. 2007;2(11):1044–51. doi:10.1097/JTO.0b013e318158eed4.PubMedCrossRef

140.

Chorostowska-Wynimko J, Skronski M, Szpechcinski A. Markery molekularne we wczesnej diagnostyce raka płuca - fakty i nadzieje. Onkol Inf. 2011;8(3):152–9.

141.

Skronski M, Szpechcinski A, Chorostowska-Wynimko J. Współczesne metody wykrywania mutacji genu EGFR jako czynnika predykcyjnego dla terapii ukierunkowanej molekularnie chorych na niedrobnokomórkowego raka płuca - czy istnieje “złoty standard” diagnostyczny? Pneumonol Alergol Pol. 2014;82(3):311–22.PubMedCrossRef

142.

Chorostowska-Wynimko J, Skroński M, Szpechcinski A. Molekularne markery prognostyczne i predykcyjne w diagnostyce niedrobnokomórkowego raka płuca. Onkol Inf. 2011;8(3):160–7.

143.

Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 2011;3(75):75ra26. doi:10.1126/scitranslmed.3002003.PubMedPubMedCentralCrossRef

144.

Ricciuti B, Mecca C, Cenci M, et al. miRNAs and resistance to EGFR-TKIs in EGFR-mutant non-small cell lung cancer: beyond ‘traditional mechanisms’ of resistance. Ecancermedicalscience. 2015;9:569. doi:10.3332/ecancer.2015.569.PubMedPubMedCentralCrossRef

145.

Zhaohui G, Jie Y, Jingqiu L, et al. Novel insights into the role of MicroRNA in lung cancer resistance to treatment and targeted therapy. Curr Cancer Drug Targets. 2014;14(3):241–58. doi:10.2174/1568009614666140305104845.CrossRef

146.

Zhang H, Su Y, Xu F, Kong J, Yu H, Qian B. Circulating microRNAs in relation to EGFR status and survival of lung adenocarcinoma in female non-smokers. PLoS One. 2013;8(11):e81408. doi:10.1371/journal.pone.0081408.PubMedPubMedCentralCrossRef

147.

Shen Y, Tang D, Yao R, et al. microRNA expression profiles associated with survival, disease progression, and response to gefitinib in completely resected non-small-cell lung cancer with EGFR mutation. Med Oncol. 2013;30(4):750. doi:10.1007/s12032-013-0750-1.PubMedCrossRef

148.

Zhao Q, Cao J, Wu Y-C, et al. Circulating miRNAs is a potential marker for gefitinib sensitivity and correlation with EGFR mutational status in human lung cancers. Am J Cancer Res. 2015;5(5):1692–705.PubMedPubMedCentral

149.

Wang S, Su X, Bai H, et al. Identification of plasma microRNA profiles for primary resistance to EGFR-TKIs in advanced non-small cell lung cancer (NSCLC) patients with EGFR activating mutation. J Hematol Oncol. 2015;8:127. doi:10.1186/s13045-015-0210-9.PubMedPubMedCentralCrossRef

150.

Li B, Ren S, Li X, et al. MiR-21 overexpression is associated with acquired resistance of EGFR-TKI in non-small cell lung cancer. Lung Cancer. 2014;83(2):146–53. doi:10.1016/j.lungcan.2013.11.003.PubMedCrossRef

151.

Kim SM, Kim JS, Kim JH, et al. Acquired resistance to cetuximab is mediated by increased PTEN instability and leads cross-resistance to gefitinib in HCC827 NSCLC cells. Cancer Lett. 2010;296(2):150–9. doi:10.1016/j.canlet.2010.04.006.PubMedCrossRef

152.

Cheng X, Chen H. Tumor heterogeneity and resistance to EGFR-targeted therapy in advanced nonsmall cell lung cancer: challenges and perspectives. Onco Targets Ther. 2014;7:1689–704. doi:10.2147/OTT.S66502.PubMedPubMedCentralCrossRef

153.

Yoshida T, Song L, Bai Y, et al. ZEB1 mediates acquired resistance to the epidermal growth factor receptor-tyrosine kinase inhibitors in non-small cell lung cancer. PLoS One. 2016;11(1):e0147344. doi:10.1371/journal.pone.0147344.PubMedPubMedCentralCrossRef

154.

Li J, Li X, Ren S, et al. miR-200c overexpression is associated with better efficacy of EGFR-TKIs in non-small cell lung cancer patients with EGFR wild-type. Oncotarget. 2014;5(17):7902–16. doi:10.18632/oncotarget.2302.PubMedPubMedCentralCrossRef

155.

Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol. 2013;8(7):823–59. doi:10.1097/JTO.0b013e318290868f.PubMedPubMedCentralCrossRef

156.

Morgensztern D, Campo MJ, Dahlberg SE, et al. Molecularly targeted therapies in non-small-cell lung cancer annual update 2014. J Thorac Oncol. 2015;10(1 Suppl 1):S1–63. doi:10.1097/JTO.0000000000000405.PubMedPubMedCentralCrossRef

157.

Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–703. doi:10.1056/NEJMoa1006448.PubMedPubMedCentralCrossRef

158.

Maione P, Sacco PC, Sgambato A, Casaluce F, Rossi A, Gridelli C. Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application. Ther Adv Med Oncol. 2015;7(5):263–73. doi:10.1177/1758834015595048.PubMedPubMedCentralCrossRef

159.

Gao HX, Yan L, Li C, Zhao LM, Liu W. miR-200c regulates crizotinib-resistant ALK-positive lung cancer cells by reversing epithelial-mesenchymal transition via targeting ZEB1. Mol Med Rep. 2016;14(5):4135–43. doi:10.3892/mmr.2016.5770.PubMedPubMedCentral

160.

Gelsomino F, Facchinetti F, Haspinger ER, et al. Targeting the MET gene for the treatment of non-small-cell lung cancer. Crit Rev Oncol/Hematol. 2014;89(2):284–99. doi:10.1016/j.critrevonc.2013.11.006.CrossRef

161.

Brighenti M. MicroRNA and MET in lung cancer. Ann Translat Med. 2015;3(5):68. doi:10.3978/j.issn.2305-5839.2015.01.26.

162.

Rokavec M, Li H, Jiang L, Hermeking H. The p53/miR-34 axis in development and disease. J Mol Cell Biol. 2014;6(3):214–30. doi:10.1093/jmcb/mju003.PubMedCrossRef

163.

Migliore C, Petrelli A, Ghiso E, et al. MicroRNAs impair MET-mediated invasive growth. Cancer Res. 2008;68(24):10128–36. doi:10.1158/0008-5472.CAN-08-2148.PubMedCrossRef

164.

Garofalo M, Romano G, Di Leva G, et al. EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nat Med. 2011;18(1):74–82. doi:10.1038/nm.2577.PubMedPubMedCentral

165.

Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov. 2013;12(11):847–65. doi:10.1038/nrd4140.PubMedPubMedCentralCrossRef

166.

Uhlmann S, Mannsperger H, Zhang JD, et al. Global microRNA level regulation of EGFR-driven cell-cycle protein network in breast cancer. Mol Syst Biol. 2012;8:570. doi:10.1038/msb.2011.100.PubMedPubMedCentralCrossRef

167.

Bader AG, Brown D, Stoudemire J, Lammers P. Developing therapeutic microRNAs for cancer. Gene Ther. 2011;18(12):1121–6. doi:10.1038/gt.2011.79.PubMedPubMedCentralCrossRef

168.

Li Z, Rana TM. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov. 2014;13(8):622–38. doi:10.1038/nrd4359.PubMedCrossRef

169.

Fortunato O, Boeri M, Verri C, Moro M, Sozzi G. Therapeutic use of MicroRNAs in lung cancer. Biomed Res Int. 2014;2014:8. doi:10.1155/2014/756975.CrossRef

170.

Takamizawa J, Konishi H, Yanagisawa K, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64(11):3753–6. doi:10.1158/0008-5472.CAN-04-0637.PubMedCrossRef

171.

Raponi M, Dossey L, Jatkoe T, et al. MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res. 2009;69(14):5776–83. doi:10.1158/0008-5472.CAN-09-0587.PubMedCrossRef

172.

Landi MT, Zhao Y, Rotunno M, et al. MicroRNA expression differentiates histology and predicts survival of lung cancer. Clin Cancer Res. 2010;16(2):430–41. doi:10.1158/1078-0432.CCR-09-1736.PubMedPubMedCentralCrossRef

173.

Xia Y, Zhu Y, Zhou X, Chen Y. Low expression of let-7 predicts poor prognosis in patients with multiple cancers: a meta-analysis. Tumour Biol. 2014;35(6):5143–8. doi:10.1007/s13277-014-1663-0.PubMedCrossRef

174.

Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 MicroRNA family. Cell. 2005;120(5):635–47. doi:10.1016/j.cell.2005.01.014.PubMedCrossRef

175.

Johnson CD, Esquela-Kerscher A, Stefani G, et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 2007;67(16):7713–22. doi:10.1158/0008-5472.CAN-07-1083.PubMedCrossRef

176.

Esquela-Kerscher A, Trang P, Wiggins JF, et al. The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle. 2008;7(6):759–64. doi:10.4161/cc.7.6.5834.PubMedCrossRef

177.

Kumar MS, Erkeland SJ, Pester RE, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci U S A. 2008;105(10):3903–8. doi:10.1073/pnas.0712321105.PubMedPubMedCentralCrossRef

178.

Gallardo E, Navarro A, Viñolas N, et al. miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogenesis. 2009;30(11):1903–9. doi:10.1093/carcin/bgp219.PubMedCrossRef

179.

Bader AG. miR-34 – a microRNA replacement therapy is headed to the clinic. Front Genet. 2012;3:120. doi:10.3389/fgene.2012.00120.PubMedPubMedCentralCrossRef

180.

Bommer GT, Gerin I, Feng Y, et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 2007;17(15):1298–307. doi:10.1016/j.cub.2007.06.068.PubMedCrossRef

181.

Kasinski AL, Slack FJ. miRNA-34 prevents cancer initiation and progression in a therapeutically resistant K-ras and p53-induced mouse model of lung adenocarcinoma. Cancer Res. 2012;72(21):5576–87. doi:10.1158/0008-5472.CAN-12-2001.PubMedPubMedCentralCrossRef

182.

Wiggins JF, Ruffino L, Kelnar K, et al. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 2010;70(14):5923–30. doi:10.1158/0008-5472.CAN-10-0655.PubMedPubMedCentralCrossRef

183.

Trang P, Wiggins JF, Daige CL, et al. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Ther. 2011;19(6):1116–22. doi:10.1038/mt.2011.48.PubMedPubMedCentralCrossRef

184.

Selcuklu SD, Donoghue Mark TA, Spillane C. miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans. 2009;37(4):918.PubMedCrossRef

185.

Seike M, Goto A, Okano T, et al. MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc Natl Acad Sci U S A. 2009;106(29):12085–90. doi:10.1073/pnas.0905234106.PubMedPubMedCentralCrossRef

186.

Lee R. Announces positive results from preclinical lung cancer study using lead anti-microRNA candidate. 2015. http://www.microlinbio.com/Microlin_PR_9-24-15.pdf. Accessed 12 Nov 2016.

187.

Trang P, Medina PP, Wiggins JF, et al. Regression of murine lung tumors by the let-7 microRNA. Oncogene. 2010;29(11):1580–7. doi:10.1038/onc.2009.445.PubMedCrossRef

188.

Kasinski AL, Kelnar K, Stahlhut C, et al. A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer. Oncogene. 2015;34(27):3547–55. doi:10.1038/onc.2014.282.PubMedCrossRef

189.

Wu Y, Crawford M, Mao Y, et al. Therapeutic delivery of MicroRNA-29b by cationic lipoplexes for lung cancer. Mol Ther Nucleic Acids. 2013;2:e84. doi:10.1038/mtna.2013.14.PubMedPubMedCentralCrossRef

190.

Bacchi CE, Ciol H, Queiroga EM, Benine LC, Silva LH, Ojopi EB. Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients. Clinics. 2012;67(5):419–24.PubMedPubMedCentralCrossRef

191.

Bouchie A. First microRNA mimic enters clinic. Nat Biotechnol. 2013;31(7):577. doi:10.1038/nbt0713-577.PubMedCrossRef

192.

Product Development Pipeline. http://www.mirnarx.com/pipeline/mirna-pipeline.html. Accessed 12 Nov 2016.

193.

Pichler M, Calin GA. MicroRNAs in cancer: from developmental genes in worms to their clinical application in patients. Br J Cancer. 2015;113(4):569–73. doi:10.1038/bjc.2015.253.PubMedPubMedCentralCrossRef

194.

van Rooij E, Kauppinen S. Development of microRNA therapeutics is coming of age. EMBO Mol Med. 2014;6(7):851–64. doi:10.15252/emmm.201100899.PubMedPubMedCentralCrossRef

195.

Chira S, Jackson CS, Oprea I, et al. Progresses towards safe and efficient gene therapy vectors. Oncotarget. 2015;6(31):30675–703. doi:10.18632/oncotarget.5169.PubMedPubMedCentral

196.

Wu Y, Crawford M, Yu B, Mao Y, Nana-Sinkam SP, Lee LJ. MicroRNA delivery by cationic lipoplexes for lung cancer therapy. Mol Pharm. 2011;8(4):1381–9. doi:10.1021/mp2002076.PubMedPubMedCentralCrossRef

197.

Bharali DJ, Khalil M, Gurbuz M, Simone TM, Mousa SA. Nanoparticles and cancer therapy: a concise review with emphasis on dendrimers. Int J Nanomedicine. 2009;4:1–7.PubMedPubMedCentralCrossRef

198.

Immordino ML, Dosio F, Cattel L. Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine. 2006;1(3):297–315.PubMedPubMedCentralCrossRef

199.

Reid G, Kao SC, Pavlakis N, et al. Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer. Epigenomics. 2016;8(8):1079–85. doi:10.2217/epi-2016-0035.PubMedCrossRef

200.

Reid G, Williams M, Kirschner MB, et al. Abstract 3976: targeted delivery of a synthetic microRNA-based mimic as an approach to cancer therapy. Cancer Res. 2015;75(15 Supplement):3976. doi:10.1158/1538-7445.am2015-3976.CrossRef

201.

MacDiarmid JA, Mugridge NB, Weiss JC, et al. Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics. Cancer Cell. 2007;11(5):431–45. doi:10.1016/j.ccr.2007.03.012.PubMedCrossRef

202.

Soutschek J, Akinc A, Bramlage B, et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature. 2004;432(7014):173–8.

203.

Chiu YL, Rana TM. siRNA function in RNAi: a chemical modification analysis. RNA. 2003;9(9):1034–48.PubMedPubMedCentralCrossRef

Title: miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives
Authors: Mateusz Florczuk
Adam Szpechcinski
Joanna Chorostowska-Wynimko
Publication date: 01-04-2017
Publisher: Springer International Publishing
Published in: Targeted Oncology / Issue 2/2017
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-017-0478-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2017

Clinical Implications of Cytotoxic T Lymphocyte Antigen-4 Expression on Tumor Cells and Tumor-Infiltrating Lymphocytes in Extrahepatic Bile Duct Cancer Patients Undergoing Surgery Plus Adjuvant Chemoradiotherapy

Erratum to: A combination of the telomerase inhibitor, BIBR1532, and paclitaxel synergistically inhibit cell proliferation in breast cancer cell lines

Exploiting microRNAs As Cancer Therapeutics

Immuno-Oncology: The Third Paradigm in Early Drug Development

The Multifaceted Roles of B Cells in Solid Tumors: Emerging Treatment Opportunities

Splenic Enlargement and Bone Marrow Hyperplasia in Patients Receiving Trastuzumab-Emtansine for Metastatic Breast Cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer