Top

Published in:

Open Access 01-12-2016 | Review

Essential role of miRNAs in orchestrating the biology of the tumor microenvironment

Authors: Jamie N. Frediani, Muller Fabbri

Published in: Molecular Cancer | Issue 1/2016

Abstract

MicroRNAs (miRNAs) are emerging as central players in shaping the biology of the Tumor Microenvironment (TME). They do so both by modulating their expression levels within the different cells of the TME and by being shuttled among different cell populations within exosomes and other extracellular vesicles. This review focuses on the state-of-the-art knowledge of the role of miRNAs in the complexity of the TME and highlights limitations and challenges in the field. A better understanding of the mechanisms of action of these fascinating micro molecules will lead to the development of new therapeutic weapons and most importantly, to an improvement in the clinical outcome of cancer patients.

Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373–83. doi:10.1083/jcb.201211138. PubMed PMID: 23420871; PMCID: PMC3575529.CrossRefPubMedPubMedCentral

Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007;318(5858):1931–4. doi:10.1126/science.1149460.CrossRefPubMed

Ambros V, Lee RC, Lavanway A, Williams PT, Jewell D. MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr Biol. 2003;13(10):807–18.CrossRefPubMed

Lin SL, Miller JD, Ying SY. Intronic microRNA (miRNA). J Biomed Biotechnol. 2006;2006(4):26818. doi:10.1155/JBB/2006/26818. PubMed PMID: 17057362; PMCID: PMC1559912.PubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

Fabbri M. Non-coding RNAs and cancer. New York: Springer; 2014.CrossRef

Umezu T, Ohyashiki K, Kuroda M, Ohyashiki JH. Leukemia cell to endothelial cell communication via exosomal miRNAs. Oncogene. 2013;32(22):2747–55. doi:10.1038/onc.2012.295.CrossRefPubMed

Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. 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. PubMed PMID: 16461460; PMCID: PMC1413718.CrossRefPubMedPubMedCentral

Yamada N, Tsujimura N, Kumazaki M, Shinohara H, Taniguchi K, Nakagawa Y, Naoe T, Akao Y. Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells. Biochim Biophys Acta. 2014;1839(11):1256–72. doi:10.1016/j.bbagrm.2014.09.002.CrossRefPubMed

10.

Mao G, Liu Y, Fang X, Fang L, Lin L, Liu X, Wang N. Tumor-derived microRNA-494 promotes angiogenesis in non-small cell lung cancer. Angiogenesis. 2015;18(3):373–82. doi:10.1007/s10456-015-9474-5.CrossRefPubMed

11.

Umezu T, Tadokoro H, Azuma K, Yoshizawa S, Ohyashiki K, Ohyashiki JH. Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1. Blood. 2014;124(25):3748–57. doi:10.1182/blood-2014-05-576116. PubMed PMID: 25320245; PMCID: PMC4263983.CrossRefPubMedPubMedCentral

12.

Zhuang G, Wu X, Jiang Z, Kasman I, Yao J, Guan Y, Oeh J, Modrusan Z, Bais C, Sampath D, Ferrara N. Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway. EMBO J. 2012;31(17):3513–23. doi:10.1038/emboj.2012.183. PubMed PMID: 22773185; PMCID: PMC3433782.CrossRefPubMedPubMedCentral

13.

Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder TT, Valastyan S, Westermann F, Speleman F, Vandesompele J, Weinberg RA. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;12(3):247–56. doi:10.1038/ncb2024. PubMed PMID: 20173740; PMCID: PMC2845545.PubMedPubMedCentral

14.

Saito K, Kondo E, Matsushita M. MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6. Nucleic Acids Res. 2011;39(14):6086–99. doi:10.1093/nar/gkr194. PubMed PMID: 21486751; PMCID: PMC3152344.CrossRefPubMedPubMedCentral

15.

Lei Z, Li B, Yang Z, Fang H, Zhang GM, Feng ZH, Huang B. Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration. PLoS One. 2009;4(10):e7629. doi:10.1371/journal.pone.0007629. PubMed PMID: 19893619; PMCID: PMC2764090.CrossRefPubMedPubMedCentral

16.

Wu Z, Cai X, Huang C, Xu J, Liu A. miR-497 suppresses angiogenesis in breast carcinoma by targeting HIF-1α. Oncol Rep. 2015. doi: 10.3892/or.2015.4529.

17.

Yan JJ, Zhang YN, Liao JZ, Ke KP, Chang Y, Li PY, Wang M, Lin JS, He XX. MiR-497 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting VEGFA and AEG-1. Oncotarget. 2015;6(30):29527–42. doi:10.18632/oncotarget.5012.PubMedPubMedCentral

18.

Zhang Z, Zhang Y, Sun XX, Ma X, Chen ZN. microRNA-146a inhibits cancer metastasis by downregulating VEGF through dual pathways in hepatocellular carcinoma. Mol Cancer. 2015;14:5. doi:10.1186/1476-4598-14-5. PubMed PMID: 25608619; PMCID: PMC4326400.CrossRefPubMedPubMedCentral

19.

Ho AS, Huang X, Cao H, Christman-Skieller C, Bennewith K, Le QT, Koong AC. Circulating miR-210 as a Novel Hypoxia Marker in Pancreatic Cancer. Transl Oncol. 2010;3(2):109–13. PubMed PMID: 20360935; PMCID: PMC2847318.CrossRefPubMedPubMedCentral

20.

Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J. hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res. 2008;14(5):1340–8. doi:10.1158/1078-0432.CCR-07-1755.CrossRefPubMed

21.

Ghosh G, Subramanian IV, Adhikari N, Zhang X, Joshi HP, Basi D, Chandrashekhar YS, Hall JL, Roy S, Zeng Y, Ramakrishnan S. Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis. J Clin Invest. 2010;120(11):4141–54. doi:10.1172/JCI42980. PubMed PMID: 20972335; PMCID: PMC2964978.CrossRefPubMedPubMedCentral

22.

Bovy N, Blomme B, Frères P, Dederen S, Nivelles O, Lion M, Carnet O, Martial JA, Noël A, Thiry M, Jérusalem G, Josse C, Bours V, Tabruyn SP, Struman I. Endothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer. Oncotarget. 2015;6(12):10253–66. doi:10.18632/oncotarget.3520. PubMed PMID: 25860935; PMCID: PMC4496353.CrossRefPubMedPubMedCentral

23.

Pecot CV, Rupaimoole R, Yang D, Akbani R, Ivan C, Lu C, Wu S, Han HD, Shah MY, Rodriguez-Aguayo C, Bottsford-Miller J, Liu Y, Kim SB, Unruh A, Gonzalez-Villasana V, Huang L, Zand B, Moreno-Smith M, Mangala LS, Taylor M, Dalton HJ, Sehgal V, Wen Y, Kang Y, Baggerly KA, Lee JS, Ram PT, Ravoori MK, Kundra V, Zhang X, Ali-Fehmi R, Gonzalez-Angulo AM, Massion PP, Calin GA, Lopez-Berestein G, Zhang W, Sood AK. Tumour angiogenesis regulation by the miR-200 family. Nat Commun. 2013;4:2427. doi:10.1038/ncomms3427. PubMed PMID: 24018975; PMCID: PMC3904438.CrossRefPubMedPubMedCentral

24.

Siragam V, Rutnam ZJ, Yang W, Fang L, Luo L, Yang X, Li M, Deng Z, Qian J, Peng C, Yang BB. MicroRNA miR-98 inhibits tumor angiogenesis and invasion by targeting activin receptor-like kinase-4 and matrix metalloproteinase-11. Oncotarget. 2012;3(11):1370–85. PubMed PMID: 23211491; PMCID: PMC3717799.CrossRefPubMedPubMedCentral

25.

Lu Z, Zhang W, Gao S, Jiang Q, Xiao Z, Ye L, Zhang X. MiR-506 suppresses liver cancer angiogenesis through targeting sphingosine kinase 1 (SPHK1) mRNA. Biochem Biophys Res Commun. 2015;468(1–2):8–13. doi:10.1016/j.bbrc.2015.11.008.CrossRefPubMed

26.

Png KJ, Halberg N, Yoshida M, Tavazoie SF. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature. 2012;481(7380):190–4. doi:10.1038/nature10661.CrossRef

27.

Jusufović E, Rijavec M, Keser D, Korošec P, Sodja E, Iljazović E, Radojević Z, Košnik M. let-7b and miR-126 are down-regulated in tumor tissue and correlate with microvessel density and survival outcomes in non--small--cell lung cancer. PLoS One. 2012;7(9):e45577. doi:10.1371/journal.pone.0045577. PubMed PMID: 23029111; PMCID: PMC3454421.CrossRefPubMedPubMedCentral

28.

He T, Qi F, Jia L, Wang S, Song N, Guo L, Fu Y, Luo Y. MicroRNA-542-3p inhibits tumour angiogenesis by targeting angiopoietin-2. J Pathol. 2014;232(5):499–508. doi:10.1002/path.4324.CrossRefPubMed

29.

Vong S, Kalluri R. The role of stromal myofibroblast and extracellular matrix in tumor angiogenesis. Genes Cancer. 2011;2(12):1139–45. doi:10.1177/1947601911423940. PubMed PMID: 22866205; PMCID: PMC3411128.CrossRefPubMedPubMedCentral

30.

Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer. 2006;6(5):392–401. doi:10.1038/nrc1877.CrossRefPubMed

31.

Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420–8. doi:10.1172/JCI39104. PubMed PMID: 19487818; PMCID: PMC2689101.CrossRefPubMedPubMedCentral

32.

Mitra AK, Zillhardt M, Hua Y, Tiwari P, Murmann AE, Peter ME, Lengyel E. MicroRNAs reprogram normal fibroblasts into cancer-associated fibroblasts in ovarian cancer. Cancer Discov. 2012;2(12):1100–8. doi:10.1158/2159-8290.CD-12-0206. PubMed PMID: 23171795; PMCID: PMC3685866.CrossRefPubMedPubMedCentral

33.

Aprelikova O, Yu X, Palla J, Wei BR, John S, Yi M, Stephens R, Simpson RM, Risinger JI, Jazaeri A, Niederhuber J. The role of miR-31 and its target gene SATB2 in cancer-associated fibroblasts. Cell Cycle. 2010;9(21):4387–98. PubMed PMID: 20980827; PMCID: PMC3055190.CrossRefPubMedPubMedCentral

34.

Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449(7162):557–63. doi:10.1038/nature06188.CrossRefPubMed

35.

Long H, Xie R, Xiang T, Zhao Z, Lin S, Liang Z, Chen Z, Zhu B. Autocrine CCL5 signaling promotes invasion and migration of CD133+ ovarian cancer stem-like cells via NF-κB-mediated MMP-9 upregulation. Stem Cells. 2012;30(10):2309–19. doi:10.1002/stem.1194.CrossRefPubMed

36.

Zhang Y, Lv D, Kim HJ, Kurt RA, Bu W, Li Y, Ma X. A novel role of hematopoietic CCL5 in promoting triple-negative mammary tumor progression by regulating generation of myeloid-derived suppressor cells. Cell Res. 2013;23(3):394–408. doi:10.1038/cr.2012.178. PubMed PMID: 23266888; PMCID: PMC3587709.CrossRefPubMedPubMedCentral

37.

Taddei ML, Cavallini L, Comito G, Giannoni E, Folini M, Marini A, Gandellini P, Morandi A, Pintus G, Raspollini MR, Zaffaroni N, Chiarugi P. Senescent stroma promotes prostate cancer progression: the role of miR-210. Mol Oncol. 2014;8(8):1729–46. doi:10.1016/j.molonc.2014.07.009.CrossRefPubMed

38.

Doldi V, Callari M, Giannoni E, D’Aiuto F, Maffezzini M, Valdagni R, Chiarugi P, Gandellini P, Zaffaroni N. Integrated gene and miRNA expression analysis of prostate cancer associated fibroblasts supports a prominent role for interleukin-6 in fibroblast activation. Oncotarget. 2015;6(31):31441–60. doi:10.18632/oncotarget.5056.PubMedPubMedCentral

39.

Li P, Shan JX, Chen XH, Zhang D, Su LP, Huang XY, Yu BQ, Zhi QM, Li CL, Wang YQ, Tomei S, Cai Q, Ji J, Li JF, Chouchane L, Yu YY, Sun FZ, Xu ZH, Liu BY, Zhu ZG. Epigenetic silencing of microRNA-149 in cancer-associated fibroblasts mediates prostaglandin E2/interleukin-6 signaling in the tumor microenvironment. Cell Res. 2015;25(5):588–603. doi:10.1038/cr.2015.51. PubMed PMID: 25916550; PMCID: PMC4423088.CrossRefPubMedPubMedCentral

40.

Josson S, Gururajan M, Sung SY, Hu P, Shao C, Zhau HE, Liu C, Lichterman J, Duan P, Li Q, Rogatko A, Posadas EM, Haga CL, Chung LW. Stromal fibroblast-derived miR-409 promotes epithelial-to-mesenchymal transition and prostate tumorigenesis. Oncogene. 2015;34(21):2690–9. doi:10.1038/onc.2014.212.CrossRefPubMed

41.

Le MT, Hamar P, Guo C, Basar E, Perdigão-Henriques R, Balaj L, Lieberman J. miR-200-containing extracellular vesicles promote breast cancer cell metastasis. J Clin Invest. 2014;124(12):5109–28. doi:10.1172/JCI75695. PubMed PMID: 25401471; PMCID: PMC4348969.CrossRefPubMedPubMedCentral

42.

Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression. Nature. 2004;432(7015):332–7. doi:10.1038/nature03096. PubMed PMID: 15549095; PMCID: PMC3050735.CrossRefPubMedPubMedCentral

43.

Musumeci M, Coppola V, Addario A, Patrizii M, Maugeri-Saccà M, Memeo L, Colarossi C, Francescangeli F, Biffoni M, Collura D, Giacobbe A, D’Urso L, Falchi M, Venneri MA, Muto G, De Maria R, Bonci D. Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer. Oncogene. 2011;30(41):4231–42. doi:10.1038/onc.2011.140.CrossRefPubMed

44.

Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D’Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14(11):1271–7. doi:10.1038/nm.1880.CrossRefPubMed

45.

Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102(39):13944–9. doi:10.1073/pnas.0506654102. PubMed PMID: 16166262; PMCID: PMC1236577.CrossRefPubMedPubMedCentral

46.

Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 2008;105(13):5166–71. doi:10.1073/pnas.0800121105. PubMed PMID: 18362358; PMCID: PMC2278188.CrossRefPubMedPubMedCentral

47.

Aprelikova O, Palla J, Hibler B, Yu X, Greer YE, Yi M, Stephens R, Maxwell GL, Jazaeri A, Risinger JI, Rubin JS, Niederhuber J. Silencing of miR-148a in cancer-associated fibroblasts results in WNT10B-mediated stimulation of tumor cell motility. Oncogene. 2013;32(27):3246–53. doi:10.1038/onc.2012.351. PubMed PMID: 22890324; PMCID: PMC3711253.CrossRefPubMedPubMedCentral

48.

Olson P, Lu J, Zhang H, Shai A, Chun MG, Wang Y, Libutti SK, Nakakura EK, Golub TR, Hanahan D. MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer. Genes Dev. 2009;23(18):2152–65. doi:10.1101/gad.1820109. PubMed PMID: 19759263; PMCID: PMC2751988.CrossRefPubMedPubMedCentral

49.

Nouraee N, Van Roosbroeck K, Vasei M, Semnani S, Samaei NM, Naghshvar F, Omidi AA, Calin GA, Mowla SJ. Expression, tissue distribution and function of miR-21 in esophageal squamous cell carcinoma. PLoS One. 2013;8(9):e73009. doi:10.1371/journal.pone.0073009. PubMed PMID: 24039846; PMCID: PMC3769386.CrossRefPubMedPubMedCentral

50.

Zhang J, Liu J, Liu Y, Wu W, Li X, Wu Y, Chen H, Zhang K, Gu L. miR-101 represses lung cancer by inhibiting interaction of fibroblasts and cancer cells by down-regulating CXCL12. Biomed Pharmacother. 2015;74:215–21. doi:10.1016/j.biopha.2015.08.013.CrossRefPubMed

51.

Bronisz A, Godlewski J, Wallace JA, Merchant AS, Nowicki MO, Mathsyaraja H, Srinivasan R, Trimboli AJ, Martin CK, Li F, Yu L, Fernandez SA, Pécot T, Rosol TJ, Cory S, Hallett M, Park M, Piper MG, Marsh CB, Yee LD, Jimenez RE, Nuovo G, Lawler SE, Chiocca EA, Leone G, Ostrowski MC. Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320. Nat Cell Biol. 2012;14(2):159–67. doi:10.1038/ncb2396. PubMed PMID: 22179046; PMCID: PMC3271169.CrossRefPubMedCentral

52.

Zhang Y, Yang P, Sun T, Li D, Xu X, Rui Y, Li C, Chong M, Ibrahim T, Mercatali L, Amadori D, Lu X, Xie D, Li QJ, Wang XF. miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis. Nat Cell Biol. 2013;15(3):284–94. doi:10.1038/ncb2690. PubMed PMID: 23396050; PMCID: PMC3672398.CrossRefPubMedPubMedCentral

53.

Farahani M, Rubbi C, Liu L, Slupsky JR, Kalakonda N. CLL Exosomes Modulate the Transcriptome and Behaviour of Recipient Stromal Cells and Are Selectively Enriched in miR-202-3p. PLoS One. 2015;10(10):e0141429. doi:10.1371/journal.pone.0141429. PubMed PMID: 26509439; PMCID: PMC4625016.CrossRefPubMedPubMedCentral

54.

Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141(1):52–67. doi:10.1016/j.cell.2010.03.015. PubMed PMID: 20371345; PMCID: PMC2862057.CrossRefPubMedPubMedCentral

55.

Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647–58. doi:10.1053/j.gastro.2007.05.022.CrossRefPubMedPubMedCentral

56.

Wang Q, Tang H, Yin S, Dong C. Downregulation of microRNA-138 enhances the proliferation, migration and invasion of cholangiocarcinoma cells through the upregulation of RhoC/p-ERK/MMP-2/MMP-9. Oncol Rep. 2013;29(5):2046–52. doi:10.3892/or.2013.2304.PubMed

57.

Chou J, Lin JH, Brenot A, Kim JW, Provot S, Werb Z. GATA3 suppresses metastasis and modulates the tumour microenvironment by regulating microRNA-29b expression. Nat Cell Biol. 2013;15(2):201–13. doi:10.1038/ncb2672. PubMed PMID: 23354167; PMCID: PMC3660859.CrossRefPubMedPubMedCentral

58.

Song N, Liu H, Ma X, Zhang S. Placental growth factor promotes metastases of ovarian cancer through MiR-543-regulated MMP7. Cell Physiol Biochem. 2015;37(3):1104–12. doi:10.1159/000430235.CrossRefPubMed

59.

Du WW, Fang L, Li M, Yang X, Liang Y, Peng C, Qian W, O’Malley YQ, Askeland RW, Sugg SL, Qian J, Lin J, Jiang Z, Yee AJ, Sefton M, Deng Z, Shan SW, Wang CH, Yang BB. MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling. J Cell Sci. 2013;126(Pt 6):1440–53. doi:10.1242/jcs.118299.CrossRefPubMed

60.

Gabriely G, Wurdinger T, Kesari S, Esau CC, Burchard J, Linsley PS, Krichevsky AM. MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol Cell Biol. 2008;28(17):5369–80. doi:10.1128/MCB.00479-08. PubMed PMID: 18591254; PMCID: PMC2519720.CrossRefPubMedPubMedCentral

61.

Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du WW, Yee AJ, Ang LC, He C, Shan SW, Yang BB. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8. Oncogene. 2011;30(7):806–21. doi:10.1038/onc.2010.465.CrossRefPubMed

62.

Hunt S, Jones AV, Hinsley EE, Whawell SA, Lambert DW. MicroRNA-124 suppresses oral squamous cell carcinoma motility by targeting ITGB1. FEBS Lett. 2011;585(1):187–92. doi:10.1016/j.febslet.2010.11.038.CrossRefPubMed

63.

Li G, Luna C, Qiu J, Epstein DL, Gonzalez P. Targeting of integrin beta1 and kinesin 2alpha by microRNA 183. J Biol Chem. 2010;285(8):5461–71. doi:10.1074/jbc.M109.037127. PubMed PMID: 19940135; PMCID: PMC2820774.CrossRefPubMedPubMedCentral

64.

Shan SW, Lee DY, Deng Z, Shatseva T, Jeyapalan Z, Du WW, Zhang Y, Xuan JW, Yee SP, Siragam V, Yang BB. MicroRNA MiR-17 retards tissue growth and represses fibronectin expression. Nat Cell Biol. 2009;11(8):1031–8. doi:10.1038/ncb1917.CrossRefPubMed

65.

Ji J, Zhao L, Budhu A, Forgues M, Jia HL, Qin LX, Ye QH, Yu J, Shi X, Tang ZY, Wang XW. Let-7g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. J Hepatol. 2010;52(5):690–7. doi:10.1016/j.jhep.2009.12.025. PubMed PMID: 20338660; PMCID: PMC2862772.CrossRefPubMedPubMedCentral

66.

Su B, Zhao W, Shi B, Zhang Z, Yu X, Xie F, Guo Z, Zhang X, Liu J, Shen Q, Wang J, Li X, Zhou L. Let-7d suppresses growth, metastasis, and tumor macrophage infiltration in renal cell carcinoma by targeting COL3A1 and CCL7. Mol Cancer. 2014;13:206. doi:10.1186/1476-4598-13-206. PubMed PMID: 25193015; PMCID: PMC4168121.CrossRefPubMedPubMedCentral

67.

Verghese ET, Drury R, Green CA, Holliday DL, Lu X, Nash C, Speirs V, Thorne JL, Thygesen HH, Zougman A, Hull MA, Hanby AM, Hughes TA. MiR-26b is down-regulated in carcinoma-associated fibroblasts from ER-positive breast cancers leading to enhanced cell migration and invasion. J Pathol. 2013;231(3):388–99. doi:10.1002/path.4248. PubMed PMID: 23939832; PMCID: PMC4030585.CrossRefPubMedPubMedCentral

68.

Zhou W, Fong MY, Min Y, Somlo G, Liu L, Palomares MR, Yu Y, Chow A, O’Connor ST, Chin AR, Yen Y, Wang Y, Marcusson EG, Chu P, Wu J, Wu X, Li AX, Li Z, Gao H, Ren X, Boldin MP, Lin PC, Wang SE. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell. 2014;25(4):501–15. doi:10.1016/j.ccr.2014.03.007. PubMed PMID: 24735924; PMCID: PMC4016197.CrossRefPubMedPubMedCentral

69.

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. doi:10.1016/j.cell.2011.02.013.CrossRefPubMed

70.

Asgharzadeh S, Salo JA, Ji L, Oberthuer A, Fischer M, Berthold F, Hadjidaniel M, Liu CW, Metelitsa LS, Pique-Regi R, Wakamatsu P, Villablanca JG, Kreissman SG, Matthay KK, Shimada H, London WB, Sposto R, Seeger RC. Clinical significance of tumor-associated inflammatory cells in metastatic neuroblastoma. J Clin Oncol. 2012;30(28):3525–32. doi:10.1200/JCO.2011.40.9169. PubMed PMID: 22927533; PMCID: 3675667.CrossRefPubMedPubMedCentral

71.

Zhang QW, Liu L, Gong CY, Shi HS, Zeng YH, Wang XZ, Zhao YW, Wei YQ. Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLoS One. 2012;7(12), e50946. doi:10.1371/journal.pone.0050946. PubMed PMID: 23284651; PMCID: PMC3532403.CrossRefPubMedPubMedCentral

72.

Jinushi M, Komohara Y. Tumor-associated macrophages as an emerging target against tumors: Creating a new path from bench to bedside. Biochim Biophys Acta. 2015;1855(2):123–30. doi:10.1016/j.bbcan.2015.01.002.PubMed

73.

Colvin EK. Tumor-associated macrophages contribute to tumor progression in ovarian cancer. Front Oncol. 2014;4:137. doi:10.3389/fonc.2014.00137. PubMed PMID: 24936477; PMCID: PMC4047518.CrossRefPubMedPubMedCentral

74.

Marelli G, Allavena P, Erreni M. Tumor-associated macrophages, multi-tasking cells in the cancer landscape. Cancer Res Frontiers. 2015;1(2):149–61.CrossRef

75.

Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, Lovat F, Fadda P, Mao C, Nuovo GJ, Zanesi N, Crawford M, Ozer GH, Wernicke D, Alder H, Caligiuri MA, Nana-Sinkam P, Perrotti D, Croce CM. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U S A. 2012;109(31):E2110–6. doi:10.1073/pnas.1209414109. PubMed PMID: 22753494; PMCID: PMC3412003.CrossRefPubMedPubMedCentral

76.

Challagundla KB, Wise PM, Neviani P, Chava H, Murtadha M, Xu T, Kennedy R, Ivan C, Zhang X, Vannini I, Fanini F, Amadori D, Calin GA, Hadjidaniel M, Shimada H, Jong A, Seeger RC, Asgharzadeh S, Goldkorn A, Fabbri M. Exosome-Mediated Transfer of microRNAs Within the Tumor Microenvironment and Neuroblastoma Resistance to Chemotherapy. J Natl Cancer Inst. 2015;107(7). doi: 10.1093/jnci/djv135.

77.

Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70. doi:10.1158/0008-5472.CAN-05-1783.CrossRefPubMed

78.

Stenvold H, Donnem T, Andersen S, Al-Saad S, Valkov A, Pedersen MI, Busund LT, Bremnes RM. High tumor cell expression of microRNA-21 in node positive non-small cell lung cancer predicts a favorable clinical outcome. BMC Clin Pathol. 2014;14(1):9. doi:10.1186/1472-6890-14-9. PubMed PMID: 24524655; PMCID: PMC3931486.CrossRefPubMedPubMedCentral

79.

Gao J, Zhang Q, Xu J, Guo L, Li X. Clinical significance of serum miR-21 in breast cancer compared with CA153 and CEA. Chin J Cancer Res. 2013;25(6):743–8. doi:10.3978/j.issn.1000-9604.2013.12.04. PubMed PMID: 24385703; PMCID: PMC3872537.PubMedPubMedCentral

80.

Wang G, Wang L, Sun S, Wu J, Wang Q. Quantitative measurement of serum microRNA-21 expression in relation to breast cancer metastasis in Chinese females. Ann Lab Med. 2015;35(2):226–32. doi:10.3343/alm.2015.35.2.226. PubMed PMID: 25729725; PMCID: PMC4330173.CrossRefPubMedPubMedCentral

81.

Toiyama Y, Takahashi M, Hur K, Nagasaka T, Tanaka K, Inoue Y, Kusunoki M, Boland CR, Goel A. Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst. 2013;105(12):849–59. doi:10.1093/jnci/djt101. PubMed PMID: 23704278; PMCID: PMC3687369.CrossRefPubMedPubMedCentral

82.

Yang M, Chen J, Su F, Yu B, Lin L, Liu Y, Huang JD, Song E. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol Cancer. 2011;10:117. doi:10.1186/1476-4598-10-117. PubMed PMID: 21939504; PMCID: PMC3190352.CrossRefPubMedPubMedCentral

83.

Lin X, Chen L, Yao Y, Zhao R, Cui X, Chen J, Hou K, Zhang M, Su F, Song E. CCL18-mediated down-regulation of miR98 and miR27b promotes breast cancer metastasis. Oncotarget. 2015;6(24):20485–99. doi:10.18632/oncotarget.4107. PubMed PMID: 26244871; PMCID: PMC4653020.CrossRefPubMedPubMedCentral

84.

Nilsson S, Möller C, Jirström K, Lee A, Busch S, Lamb R, Landberg G. Downregulation of miR-92a is associated with aggressive breast cancer features and increased tumour macrophage infiltration. PLoS One. 2012;7(4), e36051. doi:10.1371/journal.pone.0036051. PubMed PMID: 22563438; PMCID: PMC3338574.CrossRefPubMedPubMedCentral

85.

Xu S, Wei J, Wang F, Kong LY, Ling XY, Nduom E, Gabrusiewicz K, Doucette T, Yang Y, Yaghi NK, Fajt V, Levine JM, Qiao W, Li XG, Lang FF, Rao G, Fuller GN, Calin GA, Heimberger AB. Effect of miR-142-3p on the M2 macrophage and therapeutic efficacy against murine glioblastoma. J Natl Cancer Inst. 2014;106(8). doi: 10.1093/jnci/dju162. PubMed PMID: 24974128; PMCID: PMC4271080.

86.

Xu Z, Zhao L, Zhu LY, He M, Zheng L, Wu Y. MicroRNA-17, 20a regulates the proangiogenic function of tumor-associated macrophages via targeting hypoxia-inducible factor 2α. PLoS One. 2013;8(10), e77890. doi:10.1371/journal.pone.0077890. PubMed PMID: 24194900; PMCID: PMC3806827.CrossRefPubMedPubMedCentral

87.

Li Y, Zhao L, Shi B, Ma S, Xu Z, Ge Y, Liu Y, Zheng D, Shi J. Functions of miR-146a and miR-222 in Tumor-associated Macrophages in Breast Cancer. Sci Rep. 2015;5:18648. doi:10.1038/srep18648. PubMed PMID: 26689540; PMCID: PMC4686897.CrossRefPubMedPubMedCentral

88.

Chaudhuri AA, So AY, Sinha N, Gibson WS, Taganov KD, O’Connell RM, Baltimore D. MicroRNA-125b potentiates macrophage activation. J Immunol. 2011;187(10):5062–8. doi:10.4049/jimmunol.1102001. PubMed PMID: 22003200; PMCID: PMC3208133.CrossRefPubMedPubMedCentral

89.

Ma S, Liu M, Xu Z, Li Y, Guo H, Ge Y, Liu Y, Zheng D, Shi J. A double feedback loop mediated by microRNA-23a/27a/24-2 regulates M1 versus M2 macrophage polarization and thus regulates cancer progression. Oncotarget. 2015. doi: 10.18632/oncotarget.6284

90.

Squadrito ML, Pucci F, Magri L, Moi D, Gilfillan GD, Ranghetti A, Casazza A, Mazzone M, Lyle R, Naldini L, De Palma M. miR-511-3p modulates genetic programs of tumor-associated macrophages. Cell Rep. 2012;1(2):141–54. doi:10.1016/j.celrep.2011.12.005.CrossRefPubMed

91.

Donatelli SS, Zhou JM, Gilvary DL, Eksioglu EA, Chen X, Cress WD, Haura EB, Schabath MB, Coppola D, Wei S, Djeu JY. TGF-β-inducible microRNA-183 silences tumor-associated natural killer cells. Proc Natl Acad Sci U S A. 2014;111(11):4203–8. doi:10.1073/pnas.1319269111. PubMed PMID: 24586048; PMCID: PMC3964044.CrossRefPubMedPubMedCentral

92.

Sun X, Zhang J, Hou Z, Han Q, Zhang C, Tian Z. miR-146a is directly regulated by STAT3 in human hepatocellular carcinoma cells and involved in anti-tumor immune suppression. Cell Cycle. 2015;14(2):243–52. doi:10.4161/15384101.2014.977112. PubMed PMID: 25607648; PMCID: PMC4352959.CrossRefPubMedPubMedCentral

93.

Tang B, Wu W, Wei X, Li Y, Ren G, Fan W. Activation of glioma cells generates immune tolerant NKT cells. J Biol Chem. 2014;289(50):34595–600. doi:10.1074/jbc.M114.614503. PubMed PMID: 25342742; PMCID: PMC4263866.CrossRefPubMedPubMedCentral

94.

Noman MZ, Janji B, Berchem G, Chouaib S. miR-210 and hypoxic microvesicles: Two critical components of hypoxia involved in the regulation of killer cells function. Cancer Lett. 2015. doi: 10.1016/j.canlet.2015.10.026.

95.

Berchem G, Noman MZ, Bosseler M, Paggetti J, Baconnais S, Lecam E, Nanbakhsh A, Moussay E, Chouaib FM, Janji B, Chouaib S. Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-beta and miR23a transfer. Onco Immunology 2015;5(4):e1062968.

96.

Yin Y, Cai X, Chen X, Liang H, Zhang Y, Li J, Wang Z, Zhang W, Yokoyama S, Wang C, Li L, Hou D, Dong L, Xu T, Hiroi T, Yang F, Ji H, Zhang J, Zen K, Zhang CY. Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth. Cell Res. 2014;24(10):1164–80. doi:10.1038/cr.2014.121. PubMed PMID: 25223704; PMCID: PMC4185347.CrossRefPubMedPubMedCentral

97.

Wang B, Wang Q, Wang Z, Jiang J, Yu SC, Ping YF, Yang J, Xu SL, Ye XZ, Xu C, Yang L, Qian C, Wang JM, Cui YH, Zhang X, Bian XW. Metastatic consequences of immune escape from NK cell cytotoxicity by human breast cancer stem cells. Cancer Res. 2014;74(20):5746–57. doi:10.1158/0008-5472.CAN-13-2563.CrossRefPubMed

98.

Xie J, Liu M, Li Y, Nie Y, Mi Q, Zhao S. Ovarian tumor-associated microRNA-20a decreases natural killer cell cytotoxicity by downregulating MICA/B expression. Cell Mol Immunol. 2014;11(5):495–502. doi:10.1038/cmi.2014.30. PubMed PMID: 24813230; PMCID: PMC4197204.CrossRefPubMedPubMedCentral

99.

Tsukerman P, Stern-Ginossar N, Gur C, Glasner A, Nachmani D, Bauman Y, Yamin R, Vitenshtein A, Stanietsky N, Bar-Mag T, Lankry D, Mandelboim O. MiR-10b downregulates the stress-induced cell surface molecule MICB, a critical ligand for cancer cell recognition by natural killer cells. Cancer Res. 2012;72(21):5463–72. doi:10.1158/0008-5472.CAN-11-2671.CrossRefPubMed

100.

Jiang H, Wang P, Li X, Wang Q, Deng ZB, Zhuang X, Mu J, Zhang L, Wang B, Yan J, Miller D, Zhang HG. Restoration of miR17/20a in solid tumor cells enhances the natural killer cell antitumor activity by targeting Mekk2. Cancer Immunol Res. 2014;2(8):789–99. doi:10.1158/2326-6066.CIR-13-0162. PubMed PMID: 24801835; PMCID: PMC4396632.CrossRefPubMedPubMedCentral

101.

Xu H, Cheung IY, Guo HF, Cheung NK. MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: potential implications for immune based therapy of human solid tumors. Cancer Res. 2009;69(15):6275–81. doi:10.1158/0008-5472.CAN-08-4517. PubMed PMID: 19584290; PMCID: PMC2719680.CrossRefPubMedPubMedCentral

102.

Heinemann A, Zhao F, Pechlivanis S, Eberle J, Steinle A, Diederichs S, Schadendorf D, Paschen A. Tumor suppressive microRNAs miR-34a/c control cancer cell expression of ULBP2, a stress-induced ligand of the natural killer cell receptor NKG2D. Cancer Res. 2012;72(2):460–71. doi:10.1158/0008-5472.CAN-11-1977.CrossRefPubMed

Title: Essential role of miRNAs in orchestrating the biology of the tumor microenvironment
Authors: Jamie N. Frediani
Muller Fabbri
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2016
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-016-0525-3

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

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2016

Erratum to: ‘Expression of granzyme B sensitizes ALK+ ALCL tumour cells to apoptosis-inducing drugs’

Clinical significance of microRNAs in chronic and acute human leukemia

Imaging metabolic heterogeneity in cancer

Higher levels of TIMP-1 expression are associated with a poor prognosis in triple-negative breast cancer

CCL18 from ascites promotes ovarian cancer cell migration through proline-rich tyrosine kinase 2 signaling

Lipocalin2 suppresses metastasis of colorectal cancer by attenuating NF-κB-dependent activation of snail and epithelial mesenchymal transition

Keynote webinar | Spotlight on antibody–drug conjugates in cancer