Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Upregulation of microRNA-3129 suppresses epithelial ovarian cancer through CD44

Cancer Gene Therapy volume 25, pages 317–325 (2018)Cite this article

Subjects

Abstract

The purpose of this work is to evaluate whether human microRNA-3129 (hsa-miR-3129) may functionally regulate cancer development, possibly through downstream target CD44 in human epithelial ovarian cancer (EOC). Direct targeting of hsa-miR-3129 on human CD44 transcript was evaluated using a dual-luciferase reporter assay. Gene expression of hsa-miR-3129 in immortal EOC cell lines was evaluated by qRT-PCR. Lentivirus-mediated hsa-miR-3129 upregulation or downregulation was conducted in SK-OV-3 and CAOV-3 cells, in which endogenous hsa-miR-3129 and CD44 expressions were then measured. In hsa-miR-3129 upregulated or downregulated EOC cells, functional assays were applied to evaluate EOC proliferation, bufalin chemoresistance in vitro, or xenotransplantation in vivo. Moreover, CD44 was ectopically overexposed in hsa-miR-3129 upregulated EOC cells to functionally evaluate the correlation between hsa-miR-3129 and CD44 in EOC. Dual-luciferase reporter assay confirmed hsa-miR-3129 directly binds CD44. QRT-PCR revealed that hsa-miR-3129 was substantially downregulated in EOC cell lines. In SK-OV-3 and CAOV-3 cells, lentivirus-induced hsa-miR-3129 upregulation downregulated CD44 whereas hsa-miR-3129 downregulation did not affect CD44 expression. Hsa-miR-3129 upregulation had significant anti-cancer effects by inhibiting EOC proliferation, increasing bufalin chemoresistance, and suppressing xenotransplantation. On the other hand, overexpressing CD44 reversed the anti-cancer functions by hsa-miR-3129 upregulation in EOC cells. In conclusion, Has-miR-3129 is a functional regulator, possibly through reverse targeting on CD44, in EOC.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. La Vecchia C. Ovarian cancer: epidemiology and risk factors. Eur J Cancer Prev. 2017;26:55–62.

    Article  Google Scholar 

  2. Schildkraut JM, Alberg AJ, Bandera EV, Barnholtz-Sloan J, Bondy M, Cote ML, et al. A multi-center population-based case-control study of ovarian cancer in African-American women: the African American Cancer Epidemiology Study (AACES). BMC Cancer. 2014;14:688.

    Article  Google Scholar 

  3. Pearce CL, Stram DO, Ness RB, Stram DA, Roman LD, Templeman C, et al. Population distribution of lifetime risk of ovarian cancer in the United States. Cancer Epidemiol Biomark Prev. 2015;24:671–6.

    Article  Google Scholar 

  4. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67:7–30.

    Article  Google Scholar 

  5. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.

    Article  Google Scholar 

  6. Liu J, Matulonis UA. New strategies in ovarian cancer: translating the molecular complexity of ovarian cancer into treatment advances. Clin Cancer Res. 2014;20:5150–6.

    Article  CAS  Google Scholar 

  7. Kotsopoulos IC, Papanikolaou A, Lambropoulos AF, Papazisis KT, Tsolakidis D, Touplikioti P, et al. Serous ovarian cancer signaling pathways. Int J Gynecol Cancer. 2014;24:410–7.

    Article  Google Scholar 

  8. Norouzi-Barough L, Sarookhani MR, Sharifi M, Moghbelinejad S, Jangjoo S, Salehi R. Molecular mechanisms of drug resistance in ovarian cancer. J Cell Physiol. 2017;233:4546–62.

    Article  Google Scholar 

  9. Braga EA, Fridman MV, Kushlinskii NE. Molecular mechanisms of ovarian carcinoma metastasis: key genes and regulatory microRNAs. Biochemistry (Moscow). 2017;82:529–41.

    Article  CAS  Google Scholar 

  10. Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, et al. Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 2008;68:4311–20.

    Article  CAS  Google Scholar 

  11. Cannistra SA, DeFranzo B, Niloff J, Ottensmeir C. Functional heterogeneity of CD44 molecules in ovarian cancer cell lines. Clin Cancer Res. 1995;1:333–42.

    CAS  PubMed  Google Scholar 

  12. Strobel T, Swanson L, Cannistra SA. In vivo inhibition of CD44 limits intra-abdominal spread of a human ovarian cancer xenograft in nude mice: a novel role for CD44 in the process of peritoneal implantation. Cancer Res. 1997;57:1228–32.

    CAS  PubMed  Google Scholar 

  13. Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis. 2015;35:3–11.

    Article  CAS  Google Scholar 

  14. Hammond SM. An overview of microRNAs. Adv Drug Deliv Rev. 2015;87:3–14.

    Article  CAS  Google Scholar 

  15. Srinivasan S, Selvan ST, Archunan G, Gulyas B, Padmanabhan P. MicroRNAs—the next generation therapeutic targets in human diseases. Theranostics. 2013;3:930–42.

    Article  CAS  Google Scholar 

  16. Bhaskaran M, Mohan M. MicroRNAs: history, biogenesis, and their evolving role in animal development and disease. Vet Pathol. 2014;51:759–74.

    Article  CAS  Google Scholar 

  17. Kinose Y, Sawada K, Nakamura K, Kimura T. The role of microRNAs in ovarian cancer. Biomed Res Int. 2014;2014:249393.

    Article  Google Scholar 

  18. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007;67:8699–707.

    Article  CAS  Google Scholar 

  19. Chen Y, Zhang L, Hao Q. Candidate microRNA biomarkers in human epithelial ovarian cancer: systematic review profiling studies and experimental validation. Cancer Cell Int. 2013;13:86.

    Article  CAS  Google Scholar 

  20. Cheng W, Liu T, Wan X, Gao Y, Wang H. MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J. 2012;279:2047–59.

    Article  CAS  Google Scholar 

  21. Liu J, Dou Y, Sheng M. Inhibition of microRNA-383 has tumor suppressive effect in human epithelial ovarian cancer through the action on caspase-2 gene. Biomed Pharmacother. 2016;83:1286–94.

    Article  CAS  Google Scholar 

  22. Yang H, Kong W, He L, Zhao JJ, O’Donnell JD, Wang J, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008;68:425–33.

    Article  CAS  Google Scholar 

  23. Abu-Halima M, Meese E, Keller A, Abdul-Khaliq H, Radle-Hurst T. Analysis of circulating microRNAs in patients with repaired Tetralogy of Fallot with and without heart failure. J Transl Med. 2017;15:156.

    Article  Google Scholar 

  24. Lim JH, Lee DE, Kim SY, Kim HJ, Kim KS, Han YJ, et al. MicroRNAs as potential biomarkers for noninvasive detection of fetal trisomy 21. J Assist Reprod Genet. 2015;32:827–37.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Dr. Yuchan Dou for his critical review on this manuscript.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130041, China

    Xiaochun Sun & Manhua Cui

  2. Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130021, China

    Xiaochun Sun, Lingling Tong, Aichen Zhang & Kun Wang

Authors
  1. Xiaochun Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manhua Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lingling Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aichen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manhua Cui.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

In this study, all works were approved by the Medical Research and Ethic Committees at the Second Hospital of Jilin University and China-Japan Union Hospital of Jilin University in Changchun, China.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, X., Cui, M., Tong, L. et al. Upregulation of microRNA-3129 suppresses epithelial ovarian cancer through CD44. Cancer Gene Ther 25, 317–325 (2018). https://doi.org/10.1038/s41417-018-0026-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41417-018-0026-1

This article is cited by

Search

Advanced search

Quick links