Skip to main content
SpringerLink
Log in

MiR-106a targets Mcl-1 to suppress cisplatin resistance of ovarian cancer A2780 cells

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

Resistance to chemotherapy is a major obstacle for the effective treatment of advanced ovarian cancer. The mechanism of chemoresistance is still poorly understood. Recently, more and more evidence showed microRNAs (miRNAs) modulated many key molecules and pathways involved in chemotherapy. microRNA-106a (miR-106a) has been implicated in many cancers, but its role in ovarian cancer and drug resistance still remains unexplored. This study was to investigate whether miR-106a mediated resistance of the ovarian cancer cell line A2780 to the chemotherapeutic agent cisplatin (DDP). The different levels of miR-106a in A2780 cells and their resistant variant A2780/DDP cells were identified by using real-time PCR. MTT assay and flow cytometry were used to analyze the effect of miR-106a on cisplatin resistance of these paired cells. Real-time PCR, Western blotting and luciferase reporter assay were applied to explore whether Mcl-1 was a target of miR-106a. As compared to A2780 cells, the expression of miR-106a was down-regulated in the cisplatin resistant cell line A2780/DDP. Moreover, knockdown of miR-106a dramatically decreased antiproliferative effects and apoptosis induced by cisplatin in A2780 cells, while overexpression of miR-106a significantly increased antiproliferative effects and apoptosis induced by cisplatin in A2780/DDP cells. Furthermore, miR-106a inhibited cell survival and cisplatin resistance through downregulating the expression of Mcl-1. Mcl-1 was a direct target of miR-106a. These results suggest that miR-106a may provide a novel mechanism for understanding cisplatin resistance in ovarian cancer by modulating Mcl-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Legge F, Ferrandina G, Salutari V, et al. Biological characterization of ovarian cancer: prognostic and therapeutic implications. Ann Oncol, 2005,16(Suppl 4):iv95–iv101

    Article  PubMed  Google Scholar 

  2. van der Burg ME, van Lent M, Buyse M, et al, The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med, 1995,332(10):629–634

    Article  PubMed  Google Scholar 

  3. Cannistra SA. Cancer of the ovary. N Engl J Med, 2004,351(24):2519–2529

    Article  PubMed  CAS  Google Scholar 

  4. Zhang C, Yao Z, Zhu M, et al. Inhibitory effects of microRNA-34a on cell migration and invasion of invasive urothelial bladder carcinoma by targeting Notch1. J Huazhong Univ Sci Technol [Med Sci], 2012,32(3): 375–382

    Article  Google Scholar 

  5. Cortes-Sempere M, Ibanez de Caceres I. microRNAs as novel epigenetic biomarkers for human cancer. Clin Transl Oncol, 2011,13(6):357–362

    Article  PubMed  CAS  Google Scholar 

  6. Pinato DJ, Graham J, Gabra H, et al. Evolving concepts in the management of drug resistant ovarian cancer: dose dense chemotherapy and the reversal of clinical platinum resistance. Cancer Treat Rev, 2013,39(2):153–160

    Article  PubMed  CAS  Google Scholar 

  7. Eitan R, Kushnir M, Lithwick-Yanai G, et al. Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients. Gynecol Oncol, 2009,114(2):253–259

    Article  PubMed  CAS  Google Scholar 

  8. Koster R, di Pietro A, Timmer-Bosscha H, et al. Cytoplasmic p21 expression levels determine cisplatin resistance in human testicular cancer. J Clin Invest, 2010,120(10):3594–3605

    Article  PubMed  CAS  Google Scholar 

  9. Dylla L, Jedlicka P. Growth-promoting role of the miR-106a approximately 363 cluster in Ewing sarcoma. PLoS One, 2013,8(4):e63032

    Article  PubMed  CAS  Google Scholar 

  10. Timoneda O, Balcells I, Cordoba S, et al. Determination of reference microRNAs for relative quantification in porcine tissues. PLoS One, 2012,7(9):e44413

    Article  PubMed  CAS  Google Scholar 

  11. Yang X, Zheng F, Xing H. The relationship between cytochrome C and the cisplatin resistance by targeting the activity of caspase-3 in ovarian cancer. Zhonghua Zhongliu Zazhi (Chinese), 2002,24(6):544–547

    CAS  Google Scholar 

  12. Kyrgiou M, Salanti G, Pavlidis N, et al. Survival benefits with diverse chemotherapy regimens for ovarian cancer: meta-analysis of multiple treatments. J Natl Cancer Inst, 2006,98(22):1655–1663

    Article  PubMed  CAS  Google Scholar 

  13. Ferrandina G, Zannoni GF, Martinelli E, et al. Class III beta-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients. Clin Cancer Res, 2006,12(9):2774–2779

    Article  PubMed  CAS  Google Scholar 

  14. Kong F, Sun C, Wang Z, et al. miR-125b confers resistance of ovarian cancer cells to cisplatin by targeting pro-apoptotic Bcl-2 antagonist killer 1. J Huazhong Univ Sci Technol [Med Sci], 2011,31(4):543–549

    Article  CAS  Google Scholar 

  15. Yang N, Kaur S, Volinia S, et al. MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res, 2008,68(24):10307–10314

    Article  PubMed  CAS  Google Scholar 

  16. Yang L, Li N, Wang H, et al. Altered microRNA expression in cisplatin-resistant ovarian cancer cells and upregulation of miR-130a associated with MDR1/ P-glycoprotein-mediated drug resistance. Oncol Rep, 2012,28(2):592–600

    PubMed  CAS  Google Scholar 

  17. Cochrane DR, Spoelstra NS, Howe EN, et al. MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol Cancer Ther, 2009,8(5):1055–1066

    Article  PubMed  CAS  Google Scholar 

  18. Cheng W, Liu T, Wan X, et al. MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J, 2012,279(11):2047–2059

    Article  PubMed  CAS  Google Scholar 

  19. Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell, 2003,113(6): 673–676

    Article  PubMed  CAS  Google Scholar 

  20. Catela Ivkovic T, Aralica G, Cacev T, et al. miR-106a overexpression and pRB downregulation in sporadic colorectal cancer. Exp Mol Pathol, 2013,94(1):148–154

    Article  PubMed  CAS  Google Scholar 

  21. Schee K, Boye K, Abrahamsen TW, et al. Clinical relevance of microRNA miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145 in colorectal cancer. BMC Cancer, 2012,12:505

    Article  PubMed  CAS  Google Scholar 

  22. Wang Z, Liu M, Zhu H, et al. miR-106a is frequently upregulated in gastric cancer and inhibits the extrinsic apoptotic pathway by targeting FAS. Mol Carcinog, 2013,52(8):634–646

    Article  PubMed  CAS  Google Scholar 

  23. Zhao S, Yang G, Mu Y, et al. MiR-106a is an independent prognostic marker in patients with glioblastoma. Neuro Oncol, 2013,15(6):707–717

    Article  PubMed  CAS  Google Scholar 

  24. Poruchynsky MS, Giannakakou P, Ward Y, et al. Accompanying protein alterations in malignant cells with a microtubule-polymerizing drug-resistance phenotype and a primary resistance mechanism. Biochem Pharmacol, 2001,62(11):1469–1480

    Article  PubMed  CAS  Google Scholar 

  25. Simonin K, Brotin E, Dufort S, et al. Mcl-1 is an important determinant of the apoptotic response to the BH3-mimetic molecule HA14-1 in cisplatin-resistant ovarian carcinoma cells. Mol Cancer Ther, 2009,8(11): 3162–3170

    Article  PubMed  CAS  Google Scholar 

  26. Yuan Z, Cao K, Lin C, et al. The p53 upregulated modulator of apoptosis (PUMA) chemosensitizes intrinsically resistant ovarian cancer cells to cisplatin by lowering the threshold set by Bcl-x(L) and Mcl-1. Mol Med, 2011,17(11-12):1262–1274

    Article  PubMed  CAS  Google Scholar 

  27. Simonin K, N’Diaye M, Lheureux S, et al. Platinum compounds sensitize ovarian carcinoma cells to ABT-737 by modulation of the Mcl-1/Noxa axis. Apoptosis, 2013,18(4):492–508

    Article  PubMed  CAS  Google Scholar 

  28. Shigemasa K, Katoh O, Shiroyama Y, et al. Increased MCL-1 expression is associated with poor prognosis in ovarian carcinomas. Jpn J Cancer Res, 2002,93(5): 542–550

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Yu-mei Rao  (饶玉梅), Hui-rong Shi  (史惠蓉) & Mei Ji  (纪 妹)

  2. Center of Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Cai-hong Chen  (陈彩虹)

Authors
  1. Yu-mei Rao  (饶玉梅)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hui-rong Shi  (史惠蓉)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mei Ji  (纪 妹)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cai-hong Chen  (陈彩虹)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu-mei Rao  (饶玉梅).

Additional information

This project was supported by the Youth Innovation Foundation of the First Affiliated Hospital of Zhengzhou University.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rao, Ym., Shi, Hr., Ji, M. et al. MiR-106a targets Mcl-1 to suppress cisplatin resistance of ovarian cancer A2780 cells. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 567–572 (2013). https://doi.org/10.1007/s11596-013-1160-5

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-013-1160-5

Key words

Search

Navigation