circRERE regulates the expression of GBX2 through miR-1299 and ZC3H13/N-methyladenosine (mA) to promote growth and invasion of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in the world. Current studies have shown that circular RNAs (circRNAs) and N-methyladenosine (mA) methylation play important roles in the progression of HCC, but further studies are needed to confirm the underlying mechanisms. The expression of circRERE was significantly upregulated in HCC cells, and its downregulation reduced HCC cell viability and invasion while increasing apoptosis. Further study showed that circRERE bound directly to miR- 1299. After downregulating the expression of circRERE, miR-1299 expression was significantly enhanced, while the expression of its downstream target gene was suppressed, indicating that circRERE promoted the expression of GBX2 through miR-1299. In addition, downregulation of circRERE expression significantly increased the mA level of GBX2 and promoted the expression of methyltransferase ZC3H13, while overexpression of ZC3H13 significantly inhibited the expression of but increased its mA methylation. circRERE could regulate the mA modification of through ZC3H13, thus promoting the expression of . was upregulated in HCC tissues, while miR-1299 and were downregulated. MiR-1299 mimics, ZC3H13 overexpression or siRNA significantly inhibited HCC cell viability, promoted apoptosis and reduced invasion; exerted the opposite effects and could reverse the regulatory effects of miR-1299 or ZC3H13 on HCC cells. Therefore, circRERE promotes the growth and invasion of HCC cells by regulating the expression of GBX2 through miR-1299 and ZC3H13/mA, indicating that it is a key circRNA in the progression of HCC.