Circular RNA circ_KIAA1429 accelerates hepatocellular carcinoma progression via the miR-133a-3p/high mobility group AT-hook 2 (HMGA2) axis in an m6A-dependent manner

Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide with high mortality rate, and the N6-methyladenosine (m6A) epigenetic modifications have been reported to be closely associated with the pathogenesis of HCC, but the detailed molecular mechanisms by which m6A regulates HCC progression have not been fully delineated. In this study, we evidenced that the m6A methyltransferase-like 3 (METTL3)-mediated m6A modification contributed to HCC aggressiveness through modulating a novel circ_KIAA1429/miR-133a-3p/HMGA2 axis. Specifically, circ_KIAA1429 was aberrantly overexpressed in HCC tissues and cells, and the expression levels of circ_KIAA1429 was positively regulated by METTL3 in HCC cells in a m6A-dependent manner. Then, functional experiments confirmed that deletion of both circ_KIAA1429 and METTL3 suppressed HCC cell proliferation, migration and cell mitosis in vitro and in vivo, and conversely, circ_KIAA1429 overexpression had opposite effects to accelerate HCC development. Furthermore, the downstream mechanisms by which circ_KIAA1429 regulated HCC progression were uncovered, and we validated that silencing of circ_KIAA1429 restrained the malignant phenotypes in HCC cells through modulating the miR-133a-3p/high mobility group AT-hook 2 (HMGA2) axis. To summarize, our study firstly investigated the involvement of a novel METTL3/m6A/circ_KIAA1429/miR-133a-3p/HMGA2 axis in regulating HCC development, which provided novel indicators for HCC diagnosis, therapy and prognosis.