Skip to main content
Log in

MiR-195 inhibits the proliferation of human cervical cancer cells by directly targeting cyclin D1

  • Original Article
  • Published:
Tumor Biology

Abstract

MicroRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed in human cervical cancer (CC). The present study was to evaluate the level of miR-195 and cyclin D1 in CC tissues and cells. We further investigated the molecular mechanisms of miR-195 and cyclin D1 in CC cell lines HeLa and SiHa. Here, we found that miR-195 expression was down-regulated in CC tissues, and HeLa and SiHa cells (all p < 0.001). By contrast, cyclin D1 was up-regulated. Furthermore, the expression of miR-195 was inversely proportional to that of cyclin D1 mRNA or protein (p = 0.013, p = 0.015, respectively). In vitro studies demonstrated that the overexpression of miR-195 played a suppressor role in the proliferation of HeLa and SiHa cells and promoted cell apoptosis. Luciferase reporter assays confirmed that miR-195 binding to the 3′-UTR regions of cyclin D1 inhibited the expression of cyclin D1 in HeLa and SiHa cells. However, the inhibitor of miR-195 promoted the expression of cyclin D1 and cell proliferation. In conclusion, our data suggest that miR-195 may have the potential role in treatment of CC patients, as well as miR-195 is a novel regulator of invasiveness and tumorigenicity in CC cells by targeting cyclin D1. MiR-195/cyclin D1 pathway may be a useful therapeutic agent in CC patients.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. Shen MR, Hsu YM, Hsu KF, Chen YF, Tang MJ, Chou CY. Insulin like growth factor 1 is a potent stimulator of cervical cancer cell invasiveness and proliferation that is modulated by alphavbeta3 integrin signaling. Carcinogenesis. 2006;27:962–71.

    Article  CAS  PubMed  Google Scholar 

  2. Pan Y, Zhang Y, Chen L, Liu Y, Feng Y, Yan J. The critical role of Rab31 in cell proliferation and apoptosis in cancer progression. Mol Neurobiol. 2015.

  3. Galloway TJ, Ridge JA. Management of squamous cancer metastatic to cervical nodes with an unknown primary site. J Clin Oncol. 2015;33(29):3328–37.

    Article  CAS  PubMed  Google Scholar 

  4. Biglia N, Bounous VE, Sgro LG, D’Alonzo M, Gallo M. Treatment of climacteric symptoms in survivors of gynaecological cancer. Maturitas. 2015;82(3):296–8.

    Article  PubMed  Google Scholar 

  5. Yan J, Zhang Y, Ren C, Shi W, Chen L. Involvement of nuclear protein C23 in activation of EGFR signaling in cervical cancer. Tumour Biol. 2015.

  6. Yanokura M, Banno K, Iida M, Irie H, Umene K, Masuda K, et al. MicroRNAS in endometrial cancer: recent advances and potential clinical applications. EXCLI J. 2015;14:190–8.

    PubMed  PubMed Central  Google Scholar 

  7. Das SS, Karmakar P, Nandi AK, Sanan-Mishra N. Small RNA mediated regulation of seed germination. Front Plant Sci. 2015;6:828.

    PubMed  PubMed Central  Google Scholar 

  8. Gardiner AS, Twiss JL, Perrone-Bizzozero NI. Competing interactions of RNA-binding proteins, microRNAs, and their targets control neuronal development and function. Biomolecules. 2015;5(4):2903–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. He JF, Luo YM, Wan XH, Jiang D. Biogenesis of MiRNA-195 and its role in biogenesis, the cell cycle, and apoptosis. J Biochem Mol Toxicol. 2011;25(6):404–8.

    Article  CAS  PubMed  Google Scholar 

  10. Chabre O, Libe R, Assie G, Barreau O, Barreau O, Bertherat J, et al. Serum miR-483-5p and miR-195 are predictive of recurrence risk in adrenocortical cancer patients. Endocr Relat Cancer. 2013;20:579–94.

    CAS  PubMed  Google Scholar 

  11. Mao JH, Zhou RP, Peng AF, Liu ZL, Huang SH, Long XH, et al. microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN. Oncol Lett. 2012;4:1125–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Lv S, Sun B, Dai C, Shi R, Zhou X, Lv W, et al. The downregulation of microRNA-146a modulates TGF-β signaling pathways activity in glioblastoma. Mol Neurobiol. 2015;52(3):1257–62.

    Article  CAS  PubMed  Google Scholar 

  13. Liu H, Ren G, Zhu L, Liu X, He X. The upregulation of miRNA-146a inhibited biological behaviors of ESCC through inhibition of IRS2. Tumour Biol. 2015.

  14. Lange C, Huttner WB, Calegari F. Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors. Cell Stem Cell. 2009;5:320e331.

    Article  Google Scholar 

  15. Yao C, Li P, Song H, Song F, Qu Y, Ma X, et al. CXCL12/CXCR4 axis upregulates twist to induce EMT in human glioblastoma. Mol Neurobiol. 2015.

  16. Tobin NP, Sims AH, Lundgren KL, Lehn S, Landberg G. Cyclin D1, Id1 and EMT in breast cancer. BMC Cancer. 2011;11:417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li K, Xu B, Xu G, Liu R. CCR7 regulates Twist to induce the epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma. Tumour Biol. 2015.

  18. Goradia A, Wasik MA, Klein-Szanto AJ, Pontano L, Gladden AB, Nuskey B, et al. Nuclear accumulation of cyclin D1 during S phase inhibits Cul4-dependent Cdt1 proteolysis and triggers p53-dependent DNA rereplication. Genes Dev. 2007;21:2908–e2922.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kaukoniemi KM, Rauhala HE, Scaravilli M, Latonen L, Annala M, Vessella RL, et al. Epigenetically altered miR-193b targets cyclin D1 in prostate cancer. Cancer Med. 2015;4(9):1417–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li X, Gong X, Chen J, Zhang J, Sun J, Guo M. miR-340 inhibits glioblastoma cell proliferation by suppressing CDK6, cyclin-D1 and cyclin-D2. Biochem Biophys Res Commun. 2015;460(3):670–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study is supported by General Program of National Natural Science Foundation of China (No. 81272866) and National Natural Science Funds for Distinguished Young Scholars (No. 81302274). We thank all the patients who were willing to be recruited in this investigation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hongbing Cai.

Ethics declarations

Conflicts of interest

None.

Additional information

Zhen Li and Hua Wang contributed equally to this work as the co-first author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Z., Wang, H., Wang, Z. et al. MiR-195 inhibits the proliferation of human cervical cancer cells by directly targeting cyclin D1. Tumor Biol. 37, 6457–6463 (2016). https://doi.org/10.1007/s13277-015-4540-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4540-6

Keywords

Navigation