miR-31 functions as an oncogene in cervical cancer
- 489 Downloads
MicroRNAs are frequently altered in numerous cancers and are critical regulators of various diseases. miR-31 has been shown to be significantly altered in a variety of cancers.
In the present study, we measured the expression level of miR-31 in cervical cancer, CIN and normal cervical tissues by real-time RT (reverse transcription)-PCR. We also analyzed the correlations between the expression level of miR-31 and the clinical characteristics in cases of cervical squamous cell carcinoma. In addition, we measured the expression of miR-31 in cervical cancer cell lines, and transfected HPV16 E6 siRNA and HPV16 E7 siRNA into SiHa cells to investigate the effects on miR-31. Finally, the effects of miR-31 on cell proliferation, migration and invasion were measured in HeLa and SiHa cells that were transfected with a miR-31 mimic or a negative control.
We found that the expression level of miR-31 was significantly higher in cervical cancer patients than in normal individuals (P < 0.05). Aberrant expression of miR-31 was positively correlated with the lymph node metastasis (LNM), vessel invasion and HPV status (P < 0.05). Additionally, miR-31 was also overexpressed in the cervical cancer-derived HeLa and SiHa cells compared with C33A cells (P < 0.05). Moreover, a relationship was found between miR-31 expression and the HPV16 oncoproteins E6/E7. Furthermore, we found that the overexpression of miR-31 can promote cell proliferation and enhance the migration and invasion abilities of cancer cells.
Our results suggested that miR-31 plays an oncogenetic role in the development and progression of cervical cancer.
KeywordsmiR-31 Cervical cancer HPV Biological function
This work was supported by National Natural Science Foundation of China (No. 81060219) and Guangxi Natural Science Foundation of China (2014GXNSFAA118266).
Conflict of interest
The authors declare no conflict of interest.
- 4.Wilting SM, Snijders PJ, Verlaat W, Jaspers A, van de Wiel MA, van Wieringen WN, Meijer GA, Kenter GG, Yi Y, le Sage C, Agami R, Meijer CJ, Steenbergen RD (2013) Altered microRNA expression associated with chromosomal changes contributes to cervical carcinogenesis. Oncogene 32:106–116CrossRefPubMedGoogle Scholar
- 11.Liu X, Sempere LF, Ouyang H, Memoli VA, Andrew AS, Luo Y, Demidenko E, Korc M, Shi W, Preis M, Dragnev KH, Li H, Direnzo J, Bak M, Freemantle SJ, Kauppinen S, Dmitrovsky E (2010) MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J Clin Invest 120:1298–1309CrossRefPubMedCentralPubMedGoogle Scholar
- 14.Rahma OE, Herrin VE, Ibrahim RA, Toubaji A, Bernstein S, Dakheel O, Steinberg SM, Abu ER, Mkrtichyan M, Berzofsky JA, Khleif SN (2014) Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer. J Transl Med 12:353CrossRefPubMedCentralPubMedGoogle Scholar
- 21.Bandi N, Zbinden S, Gugger M, Arnold M, Kocher V, Hasan L, Kappeler A, Brunner T, Vassella E (2009) miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer. Cancer Res 69:5553–5559CrossRefPubMedGoogle Scholar
- 22.Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D’Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R (2008) The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14:1271–1277CrossRefPubMedGoogle Scholar