MicroRNA-29a inhibits cell proliferation and arrests cell cycle by modulating p16 methylation in cervical cancer.

Cervical cancer is the second most common gynecological malignancy. Accumulating evidence has suggested that microRNAs (miRNAs) are involved in the occurrence and development of cervical cancer. The present study aimed to investigate the function and underlying molecular mechanism of microRNA (miRNA/miR)-29a in cervical cancer. Reverse transcription-quantitative PCR and methylation-specific PCR were used to examine the expression of miR-29a and methylated status of p16 promoter, respectively. Cell Counting Kit-8 analysis and flow cytometry were performed to evaluate cell viability and cycle, respectively. Dual-luciferase reporter assay was performed to verify the interaction between miR-29a and its targets. Western blot analysis was performed to detect the protein levels of DNA methyltransferases (DNMT)3A and DNMT3B. The results demonstrated that miR-29a expression was downregulated in cervical cancer tissues and cells, and negatively correlated with p16 promoter hypermethylation. Furthermore, cell experiments confirmed that miR-29a suppressed cell proliferation and induced cell cycle arrest in HeLa and C-33A cells. Mechanically, miR-29a restored normal methylation pattern of the p16 gene by sponging DNMT3A and DNMT3B. Taken together, the results of the present study demonstrated the epigenetic regulation of tumor suppressor p16 by miR-29a as a unique mechanism, thus providing a rationale for the development of miRNA-based strategies in the treatment of cervical cancer.