Advertisement

Tumor Biology

, Volume 37, Issue 5, pp 6457–6463 | Cite as

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

  • Zhen Li
  • Hua Wang
  • Zhiqiang Wang
  • Hongbing Cai
Original Article

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.

Keywords

MiR-195 Cyclin D1 Cervical cancer 

Notes

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.

Compliance with ethical standards

Conflicts of interest

None.

References

  1. 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.CrossRefPubMedGoogle Scholar
  2. 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.Google Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.Google Scholar
  6. 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.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Das SS, Karmakar P, Nandi AK, Sanan-Mishra N. Small RNA mediated regulation of seed germination. Front Plant Sci. 2015;6:828.PubMedPubMedCentralGoogle Scholar
  8. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 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.PubMedPubMedCentralGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.Google Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.Google Scholar
  16. 16.
    Tobin NP, Sims AH, Lundgren KL, Lehn S, Landberg G. Cyclin D1, Id1 and EMT in breast cancer. BMC Cancer. 2011;11:417.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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.Google Scholar
  18. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Zhen Li
    • 1
  • Hua Wang
    • 2
  • Zhiqiang Wang
    • 1
  • Hongbing Cai
    • 1
  1. 1.Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological BehaviorsHubei Cancer Clinical Study CenterWuhanChina
  2. 2.Department of Obstetrics and GynecologyXiangyang First People’s Hospital, Affiliated Hospital of Hubei University of MedicineXiangyangChina

Personalised recommendations