Tumor Biology

, Volume 36, Issue 5, pp 3381–3387 | Cite as

MicroRNA-181 functions as a tumor suppressor in non-small cell lung cancer (NSCLC) by targeting Bcl-2

Research Article

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs frequently dysregulated in human malignancies. In this study, we analyzed the global expression profile of miR-181 in non-small cell lung cancer (NSCLC), as its participation in some other types of cancer has been suggested by previous reports. We found that miR-181 was downregulated both in NSCLC tissues and cell lines. Overexpression of miR-181evidently inhibited A549 cell proliferation, migration, and invasion and promotes cell apoptosis. Moreover, we also found miR-181 reduction was associated with increased Bcl-2 levels and miR-181 was further suggested to exert its pro-apoptotic function mainly through targeting Bcl-2 expression. Taken together, our study implicates important roles of miR-181 in lung cancer pathogenesis and implicates its potential application in cancer therapy.

Keywords

NSCLC miR-181 Bcl-2 Apoptosis Lung cancer 

Notes

Conflicts of interest

None

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics. CA-Cancer J Clin. 2012;62:10–29.CrossRefPubMedGoogle Scholar
  2. 2.
    Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer. 2006;6:449–58.CrossRefPubMedGoogle Scholar
  3. 3.
    Van Rooij E, Purcell AL, Levin AA. Developing microRNA therapeutics. Circ Res. 2012;110:496–507.CrossRefPubMedGoogle Scholar
  4. 4.
    Engels BM, Hutvagner G. Principles and effects of microRNA-mediated post-transcriptional gene regulation. Oncogene. 2006;25:6163–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Bartel DP. MicroRNAs genomics, biogenesis, mechanism and function. Cell. 2004;116:281–97.CrossRefPubMedGoogle Scholar
  6. 6.
    Chitwood DH, Timmermans MC. Small RNAs are on the move. Nature. 2010;67:415–9.CrossRefGoogle Scholar
  7. 7.
    Chen CZ. MicroRNAs as oncogenes and tumor suppressors. New Engl J Med. 2005;353:1768–71.CrossRefPubMedGoogle Scholar
  8. 8.
    Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466:835–40.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Dostie J, Mourelatos Z, Yang M, Sharma A, Dreyfuss G. Numerous microRNPs in neuronal cells containing novel microRNAs. RNA. 2003;9:180–6.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ryan DG, Oliveira-Fernandes M, Lavker RM. Micro-RNAs of the mammalian eye display distinct and overlapping tissue specificity. Mol Vis. 2006;12:1175–84.PubMedGoogle Scholar
  11. 11.
    Naguibneva I, Ameyar-Zazoua M, Polesskaya A, Ait-Si-Ali S, Groisman R, Souidi M, et al. The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol. 2006;8:278–84.CrossRefPubMedGoogle Scholar
  12. 12.
    Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004;303:83–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Georgantas III RW, Hildreth R, Morisot S, Alder J, Liu C, Heimfeld S, et al. CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci U S A. 2007;104:2750–5.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Ji J, Yamashita T, Budhu A, Jia H, Li C, Deng C, et al. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology. 2009;50:472–80.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Shi L, Cheng Z, Zhang J, Li R, Zhao P, Fu Z, et al. Hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res. 2008;1236:185–93.CrossRefPubMedGoogle Scholar
  16. 16.
    Bottoni A, Zatelli MC, Ferracin M, Tagliati F, Piccin D, Vignali C, et al. Identification of differentially expressed microRNAs by microarray: a possible role for microRNA genes in pituitary adenomas. J Cell Physiol. 2007;210:370–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Visone R, Rassenti LZ, Veronese A, Taccioli C, Costinean S, Aguda BD, et al. Karyotype specific microRNA signature in chronic lymphocytic leukemia. Blood. 2009;144:3872–9.CrossRefGoogle Scholar
  18. 18.
    Gao W, Yu Y, Cao H, Shen H, Li X, Pan S, et al. Deregulated expression of miR-21, miR-143 and miR-181a in non small cell lung cancer is related to clinicopathologic characteristics or patient prognosis. Biomed Pharmacother. 2010;64:399–408.CrossRefPubMedGoogle Scholar
  19. 19.
    Zhu W, Shan X, Wang T, Shu YQ, Liu P. MiR-181b modulates multidrug resistance by targeting BCL2 in human cancer cell lines. Int J Cancer. 2010. doi: 10.1002/ijc.25260.Google Scholar
  20. 20.
    Su H, Yang J, Xu T, Huang J, Xu L, Yuan Y, et al. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res. 2009;69:1135–42.CrossRefPubMedGoogle Scholar
  21. 21.
    Bhatavdekar JM, Patel DD, Ghosh N, Chikhlikar PR, Trivedi TI, Suthar TP, et al. Coexpression of Bcl-2, c-Myc, and p53 oncoproteins as prognostic discriminants in patients with colorectal carcinoma. Dis Colon Rectum. 1997;40:785–90.CrossRefPubMedGoogle Scholar
  22. 22.
    Merritt AJ, Potten CS, Watson AJ, Loh DY, Nakayama K, Hickman JA. Differential expression of Bcl-2 in intestinal epithelia correlation with ttenuationof apoptosis in colonic crypts and the incidence of colonic neoplasia. J Cell Sci. 1995;108:2261–71.PubMedGoogle Scholar
  23. 23.
    Hummel R, Hussey DJ, Haier J. MicroRNAs predictors and modifiers of chemo-and radiotherapy in different tumor types. Eur J Cancer. 2010;46:298–311.CrossRefPubMedGoogle Scholar
  24. 24.
    Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. Micro-RNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci. 2006;103:2257–61.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Mishra PJ, Merlino G. MicroRNA reexpression as differentiation therapy in cancer. J Clin Invest. 2009;119:2119–23.PubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ping Huang
    • 1
  • Bo Ye
    • 1
  • Yu Yang
    • 1
  • Jianxin Shi
    • 1
  • Heng Zhao
    • 1
  1. 1.Department of Thoracic Surgery, Shanghai Chest HospitalShanghai Jiaotong UniversityShanghaiChina

Personalised recommendations