Top

Published in:

01-01-2016 | Review

Aberrant regulation of miR-15b in human malignant tumors and its effects on the hallmarks of cancer

Authors: Ci Zhao, Guanyu Wang, Yuanyuan Zhu, Xiaobo Li, Feihu Yan, Chunhui Zhang, Xiaoyi Huang, Yanqiao Zhang

Published in: Tumor Biology | Issue 1/2016

Abstract

MicroRNAs encoded by the miR-15b/16-2 cluster act as tumor suppressors. Aberrant regulation of miR-15b in human malignant tumors is reportedly involved in cancer development, contributing to cell death, reduced proliferation, angiogenesis and metastasis resistance, metabolism reprogramming, genome instability, and tumor-associated inflammation. In this review, we summarize the mechanisms involved in regulating miR-15b expression in mammalian tumors and discuss the effects of miR-15b dysregulation on the hallmarks of cancer and highlight its role as a potentially valuable target for future cancer therapeutic strategies.

Yue J, Tigyi G. Conservation of mir-15a/16-1 and mir-15b/16-2 clusters. Mamm Genome. 2010;21:88–94.CrossRefPubMed

Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of microRNA genes mir15 and mir16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99:15524–9.CrossRefPubMedPubMedCentral

Kim YK, Kim VN. Processing of intronic microRNAs. EMBO J. 2007;26:775–83.CrossRefPubMedPubMedCentral

Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009;10:126–39.CrossRefPubMed

Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell. 2003;115:787–98.CrossRefPubMed

Graves P, Zeng Y. Biogenesis of mammalian microRNAs: a global view. Genomics Proteomics Bioinformatics. 2012;10:239–45.CrossRefPubMedPubMedCentral

Myklebust MP, Bruland O, Fluge O, Skarstein A, Balteskard L, Dahl O. MicroRNA-15b is induced with e2f-controlled genes in hpv-related cancer. Br J Cancer. 2011;105:1719–25.CrossRefPubMedPubMedCentral

Ofir M, Hacohen D, Ginsberg D. Mir-15 and mir-16 are direct transcriptional targets of e2f1 that limit e2f-induced proliferation by targeting cyclin E. Mol Cancer Res. 2011;9:440–7.CrossRefPubMed

Bueno MJ, Gomez de Cedron M, Laresgoiti U, Fernandez-Piqueras J, Zubiaga AM, Malumbres M. Multiple e2f-induced microRNAs prevent replicative stress in response to mitogenic signaling. Mol Cell Biol. 2010;30:2983–95.CrossRefPubMedPubMedCentral

10.

Subhawong AP, Subhawong T, Nassar H, Kouprina N, Begum S, Vang R, et al. Most basal-like breast carcinomas demonstrate the same rb-/p16+ immunophenotype as the hpv-related poorly differentiated squamous cell carcinomas which they resemble morphologically. Am J Surg Pathol. 2009;33:163–75.CrossRefPubMedPubMedCentral

11.

Dick FA, Rubin SM. Molecular mechanisms underlying rb protein function. Nat Rev Mol Cell Biol. 2013;14:297–306.CrossRefPubMedPubMedCentral

12.

Liu X, Gu X, Sun L, Flowers AB, Rademaker AW, Zhou Y, et al. Downregulation of smurf2, a tumor-suppressive ubiquitin ligase, in triple-negative breast cancers: Involvement of the rb-microRNA axis. BMC Cancer. 2014;14:57.CrossRefPubMedPubMedCentral

13.

Wilting SM, Snijders PJ, Verlaat W, Jaspers A, van de Wiel MA, van Wieringen WN, et al. Altered microRNA expression associated with chromosomal changes contributes to cervical carcinogenesis. Oncogene. 2013;32:106–16.CrossRefPubMed

14.

Rahman M, Lovat F, Romano G, Calore F, Acunzo M, Bell EH, et al. Mir-15b/16-2 regulates factors that promote p53 phosphorylation and augments the DNA damage response following radiation in the lung. J Biol Chem. 2014;289:26406–16.CrossRefPubMedPubMedCentral

15.

Li G, Miskimen KL, Wang Z, Xie XY, Brenzovich J, Ryan JJ, et al. Stat5 requires the n-domain for suppression of mir15/16, induction of bcl-2, and survival signaling in myeloproliferative disease. Blood. 2010;115:1416–24.CrossRefPubMedPubMedCentral

16.

Liu J, Yang L, Zhang J, Zhang J, Chen Y, Li K, et al. Knock-down of ndrg2 sensitizes cervical cancer hela cells to cisplatin through suppressing bcl-2 expression. BMC Cancer. 2012;12:370.CrossRefPubMedPubMedCentral

17.

Polytarchou C, Iliopoulos D, Struhl K. An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state. Proc Natl Acad Sci U S A. 2012;109:14470–5.CrossRefPubMedPubMedCentral

18.

Qian S, Ding JY, Xie R, An JH, Ao XJ, Zhao ZG, et al. MicroRNA expression profile of bronchioalveolar stem cells from mouse lung. Biochem Biophys Res Commun. 2008;377:668–73.CrossRefPubMed

19.

Cory S, Adams JM. The bcl2 family: Regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647–56.CrossRefPubMed

20.

Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, et al. Mir-15b and mir-16 modulate multidrug resistance by targeting bcl2 in human gastric cancer cells. Int J Cancer. 2008;123:372–9.CrossRefPubMed

21.

Chung GE, Yoon JH, Myung SJ, Lee JH, Lee SH, Lee SM, et al. High expression of microrna-15b predicts a low risk of tumor recurrence following curative resection of hepatocellular carcinoma. Oncol Rep. 2010;23(1):113–9.PubMed

22.

Sun H, Meng X, Han J, Zhang Z, Wang B, Bai X, et al. Anti-cancer activity of dha on gastric cancer—an in vitro and in vivo study. Tumour Biol. 2013;34:3791–800.CrossRefPubMed

23.

Shen J, Wan R, Hu G, Yang L, Xiong J, Wang F, et al. Mir-15b and mir-16 induce the apoptosis of rat activated pancreatic stellate cells by targeting bcl-2 in vitro. Pancreatology. 2012;12:91–9.CrossRefPubMed

24.

Fleming NH, Zhong J, da Silva IP, Vega-Saenz de Miera E, Brady B, Han SW, et al. Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients. Cancer. 2015;121:51–9.CrossRefPubMed

25.

Xia H, Qi Y, Ng SS, Chen X, Chen S, Fang M, et al. MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells. Biochem Biophys Res Commun. 2009;380:205–10.CrossRefPubMed

26.

Sun G, Shi L, Yan S, Wan Z, Jiang N, Fu L, et al. Mir-15b targets cyclin d1 to regulate proliferation and apoptosis in glioma cells. Biomed Res Int. 2014;2014:687826.PubMedPubMedCentral

27.

Kamat AA, Merritt WM, Coffey D, Lin YG, Patel PR, Broaddus R, et al. Clinical and biological significance of vascular endothelial growth factor in endometrial cancer. Clin Cancer Res. 2007;13:7487–95.CrossRefPubMed

28.

Chan LS, Yue PY, Wong YY, Wong RN. Microrna-15b contributes to ginsenoside-rg1-induced angiogenesis through increased expression of vegfr-2. Biochem Pharmacol. 2013;86:392–400.CrossRefPubMed

29.

Zheng X, Chopp M, Lu Y, Buller B, Jiang F. Mir-15b and mir-152 reduce glioma cell invasion and angiogenesis via nrp-2 and mmp-3. Cancer Lett. 2013;329:146–54.CrossRefPubMed

30.

Geretti E, Klagsbrun M. Neuropilins: Novel targets for anti-angiogenesis therapies. Cell Adh Migr. 2007;1:56–61.CrossRefPubMedPubMedCentral

31.

Liu Z, Yang D, Xie P, Ren G, Sun G, Zeng X, et al. Mir-106b and mir-15b modulate apoptosis and angiogenesis in myocardial infarction. Cell Physiol Biochem. 2012;29:851–62.CrossRefPubMed

32.

Karaa ZS, Iacovoni JS, Bastide A, Lacazette E, Touriol C, Prats H. The vegf ireses are differentially susceptible to translation inhibition by mir-16. RNA. 2009;15:249–54.CrossRefPubMedPubMedCentral

33.

Pescador N, Perez-Barba M, Ibarra JM, Corbaton A, Martinez-Larrad MT, Serrano-Rios M. Serum circulating microRNA profiling for identification of potential type 2 diabetes and obesity biomarkers. PLoS One. 2013;8, e77251.CrossRefPubMedPubMedCentral

34.

Ye EA, Steinle JJ. Mir-15b/16 protects primary human retinal microvascular endothelial cells against hyperglycemia-induced increases in tumor necrosis factor alpha and suppressor of cytokine signaling 3. J Neuroinflammation. 2015;12:44.CrossRefPubMedPubMedCentral

35.

Zhang Y, Cheng X, Lu Z, Wang J, Chen H, Fan W, et al. Upregulation of mir-15b in nafld models and in the serum of patients with fatty liver disease. Diabetes Res Clin Pract. 2013;99:327–34.CrossRefPubMed

36.

Davidson LA, Wang N, Shah MS, Lupton JR, Ivanov I, Chapkin RS. N-3 polyunsaturated fatty acids modulate carcinogen-directed non-coding microRNA signatures in rat colon. Carcinogenesis. 2009;30:2077–84.CrossRefPubMedPubMedCentral

37.

Nishi H, Ono K, Iwanaga Y, Horie T, Nagao K, Takemura G, et al. MicroRNA-15b modulates cellular atp levels and degenerates mitochondria via arl2 in neonatal rat cardiac myocytes. J Biol Chem. 2010;285:4920–30.CrossRefPubMed

38.

Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.CrossRefPubMedPubMedCentral

39.

Favreau AJ, Sathyanarayana P. Mir-590-5p, mir-219-5p, mir-15b and mir-628-5p are commonly regulated by il-3, gm-csf and g-csf in acute myeloid leukemia. Leuk Res. 2012;36:334–41.CrossRefPubMed

40.

Baraniskin A, Kuhnhenn J, Schlegel U, Maghnouj A, Zollner H, Schmiegel W, et al. Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma. Neuro Oncol. 2012;14:29–33.CrossRefPubMed

41.

Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, et al. Circulating mir-15b and mir-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012;2, e000825.CrossRefPubMedPubMedCentral

42.

Jiang X, Du L, Wang L, Li J, Liu Y, Zheng G, et al. Serum microRNA expression signatures identified from genome-wide microRNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer. Int J Cancer. 2015;136:854–62.CrossRefPubMed

43.

Komatsu S, Ichikawa D, Hirajima S, Kawaguchi T, Miyamae M, Okajima W, et al. Plasma microRNA profiles: Identification of mir-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinoma. Br J Cancer. 2014;111:1614–24.CrossRefPubMedPubMedCentral

44.

Satzger I, Mattern A, Kuettler U, Weinspach D, Voelker B, Kapp A, et al. MicroRNA-15b represents an independent prognostic parameter and is correlated with tumor cell proliferation and apoptosis in malignant melanoma. Int J Cancer. 2010;126:2553–62.PubMed

45.

Aslam MI, Venkatesh J, Jameson JS, West K, Pringle JH, Singh B. MicroRNA expression profiling based identification of high risk dukes' stage b colorectal cancer: a preliminary study. Colorectal Dis. 2014.

46.

Medina-Villaamil V, Martinez-Breijo S, Portela-Pereira P, Quindos-Varela M, Santamarina-Cainzos I, Anton-Aparicio LM, et al. Circulating microRNAs in blood of patients with prostate cancer. Actas Urol Esp. 2014;38:633–9.CrossRefPubMed

47.

Wang L, Zhu MJ, Ren AM, Wu HF, Han WM, Tan RY, et al. A ten-microRNA signature identified from a genome-wide microRNA expression profiling in human epithelial ovarian cancer. PLoS One. 2014;9, e96472.CrossRefPubMedPubMedCentral

48.

Huang YH, Lin KH, Chen HC, Chang ML, Hsu CW, Lai MW, et al. Identification of postoperative prognostic microRNA predictors in hepatocellular carcinoma. PLoS One. 2012;7, e37188.CrossRefPubMedPubMedCentral

49.

Hennessey PT, Sanford T, Choudhary A, Mydlarz WW, Brown D, Adai AT, et al. Serum microRNA biomarkers for detection of non-small cell lung cancer. PLoS One. 2012;7, e32307.CrossRefPubMedPubMedCentral

50.

Jones KB, Salah Z, Del Mare S, Galasso M, Gaudio E, Nuovo GJ, et al. Mirna signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. 2012;72:1865–77.CrossRefPubMedPubMedCentral

51.

Lu YC, Chen YJ, Wang HM, Tsai CY, Chen WH, Huang YC, et al. Oncogenic function and early detection potential of miRNA-10b in oral cancer as identified by microRNA profiling. Cancer Prev Res (Phila). 2012;5:665–74.CrossRef

52.

Garzon R, Pichiorri F, Palumbo T, Visentini M, Aqeilan R, Cimmino A, et al. MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia. Oncogene. 2007;26:4148–57.CrossRefPubMed

53.

Zhang Y, Li M, Wang H, Fisher WE, Lin PH, Yao Q, et al. Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time pcr analysis. World J Surg. 2009;33:698–709.CrossRefPubMedPubMedCentral

54.

Mairinger FD, Ting S, Werner R, Walter RF, Hager T, Vollbrecht C, et al. Different micro-RNA expression profiles distinguish subtypes of neuroendocrine tumors of the lung: Results of a profiling study. Mod Pathol. 2014;27:1632–40.CrossRefPubMed

55.

Sun L, Yao Y, Liu B, Lin Z, Lin L, Yang M, et al. Mir-200b and mir-15b regulate chemotherapy-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting bmi1. Oncogene. 2012;31:432–45.CrossRefPubMed

56.

Wu CS, Yen CJ, Chou RH, Chen JN, Huang WC, Wu CY, et al. Downregulation of microRNA-15b by hepatitis b virus x enhances hepatocellular carcinoma proliferation via fucosyltransferase 2-induced globo h expression. Int J Cancer. 2014;134:1638–47.CrossRefPubMed

57.

Kim S, Kang H. Mir-15b induced by platelet-derived growth factor signaling is required for vascular smooth muscle cell proliferation. BMB Rep. 2013;46:550–4.CrossRefPubMedPubMedCentral

58.

Zhao Z, Zhang L, Yao Q, Tao Z. Mir-15b regulates cisplatin resistance and metastasis by targeting pebp4 in human lung adenocarcinoma cells. Cancer Gene Ther. 2015;22:108–14.CrossRefPubMed

59.

Weirauch U, Beckmann N, Thomas M, Grünweller A, Huber K, Bracher F, et al. Functional role and therapeutic potential of the pim-1 kinase in colon carcinoma. Neoplasia. 2013;15:783–IN728.CrossRefPubMedPubMedCentral

60.

Loayza-Puch F, Yoshida Y, Matsuzaki T, Takahashi C, Kitayama H, Noda M. Hypoxia and ras-signaling pathways converge on, and cooperatively downregulate, the reck tumor-suppressor protein through microRNAs. Oncogene. 2010;29:2638–48.CrossRefPubMed

Title: Aberrant regulation of miR-15b in human malignant tumors and its effects on the hallmarks of cancer
Authors: Ci Zhao
Guanyu Wang
Yuanyuan Zhu
Xiaobo Li
Feihu Yan
Chunhui Zhang
Xiaoyi Huang
Yanqiao Zhang
Publication date: 01-01-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 1/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4269-2

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 medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2016

Diagnostic and prognostic significance of secretory clusterin expression in patients with hepatocellular carcinoma

CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma

Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line

The role of TARBP2 in the development and progression of cancers

CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo

Human topoisomerase II alpha as a prognostic biomarker in cancer chemotherapy

Keynote webinar | Spotlight on antibody–drug conjugates in cancer