Up-regulation of miR-20a by HPV16 E6 exerts growth-promoting effects by targeting PDCD6 in cervical carcinoma cells.

OBJECTIVE:MicroRNAs (miRNAs/miRs) have been reported to participate in progression of multiple tumors including cervical cancer. High-risk human papillomavirus (HPV) type 16 (HPV16) is the most common and lethal HPV type, leading to exceeding 50% of cervical cancer cases. However, the relationship between miRNA and HPV-induced cervical carcinogenesis remains elusive. RESULTS:Here, HPV16 E6 positively regulated miR-20a expression. Overexpression of miR-20a showed growth-promoting effects on C33A cells (HPV16-negative), and knockdown of miR-20a showed growth-inhibitory effects on CaSki cells (HPV16-positive). In addition, PDCD6 was identified as a target gene of miR-20a. Overexpression of PDCD6 exerted growth-inhibitory effects (opposite to miR-20a overexpression), which could be reversed by miR-20a overexpression. More importantly, activation of AKT and p38 was observed in C33A cells overexpressing miR-20a, and the growth-promoting action of miR-20a could be abated by p38 inhibition. CONCLUSION:Up-regulation of miR-20a by HPV16 E6 exerted growth-promoting effects by targeting PDCD6 in cervical carcinoma cells. This study demonstrated miR-20a might be a potential therapeutic target in HPV16 E6 infection type of cervical cancer.

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