N6-methyladenosine modified AFAP1-AS1 accelerates hepatocellular carcinoma proliferation and migration via miR-195-5p/KIAA1429 feedback loop

Abstract

Hepatocellular carcinoma (HCC) acts as a dominating malignant tumor with high-mortality rate and poor prognosis. Emerging evidence suggests that N6-methyladenosine (m6A) plays critical roles in HCC progression. However, function of m6A and lncRNA in HCC progression requires further clarification. In our study, we found that AFAP1-AS1, a m6A-modified lncRNA, substantially elevated in the HCC cells and correlated with poor prognosis. Interestingly, AFAP1-AS1 had m6A modification site and m6A writer KIAA1429 bound with the m6A site to enhance AFAP1-AS1 stability. Functionally, AFAP1-AS1 promoted HCC migration/ proliferation and knockdown of AFAP1-AS1 repressed the tumor growth. Mechanistically, AFAP1-AS1 up-regulated KIAA1429 expression through sponging miR-195-5p, forming positive feedback of KIAA1429/m6A/AFAP1-AS1/miR-195-5p. In summary, our study reveals a new mechanism for AFAP1-AS1-promoted HCC progression, contributing to overcoming HCC tumorigenesis.