HPV16+ -miRNAs in cervical cancer and the anti-tumor role played by miR-5701

Abstract

Background: The early diagnosis of cervical cancer is difficult, resulting in an unsatisfactory prognosis. The present study aimed to explore the expression of HPV16-related microRNAs (miRNAs) in the serum of Uygur cervical cancer in Sinkiang and analyze the miRNAs showing different expression.

Methods: The serum of 30 HPV16 positive (HPV16Pos) and 30 negative patients (HPV16Neg) was collected and then the differentially expressed miRNAs were screened out by function and pathway enrichment analyses. Next, the cervical cancer cells were cultured. miR-5701-mimic and inhibitor were transfected into cells. The level of miR-5701 was detected by a quantitative reverse transcriptase-polymerase chain reaction. The proliferation of cells was detected using a Cell Counting Kit-8 assay. Western blotting was used to measure the expression of THBS4.

Results: We identified three up-regulated miRNAs (hsa-miR-1291, hsa-miR-144-5p and hsa-miR-5701) and seven down-regulated known-miRNAs (hsa-miR-21-5p, hsa-miR-101-3p, hsa-miR-370-3p, hsa-miR-151a-3p, hsa-miR-144-3p, hsa-miR-199a-3p and hsa-miR-199b-3p) relative to HPV16Neg. The mitogen-activated protein kinase signal pathway is predicted to be a key mechanism of HPV16-related cervical cancer. Furthermore, miR-5701 inhibits the proliferation of cervical cancer cells and suppresses the expression of THBS4 (P < 0.05), which was confirmed as a target gene of miR-5701.

Conclusions: In the present study, we confirm 10 differentially expressed miRNAs that could be potential markers or therapeutic targets of cervical cancer. miR-5701 inhibits the proliferation of cervical cancer cells and the expression of its target gene THBS4.

Keywords: MAPK signaling pathway; THBS4; cervical cancer; differentially expressed miRNAs; miR-5701.