circ_KIAA1429 accelerates hepatocellular carcinoma advancement through the mechanism of mA-YTHDF3-Zeb1.

AIMS

Hepatocellular carcinoma (HCC), one of the most common cancer, causes the fourth cancer-related deaths around the world. N6-methyladenosine (mA) has been reported to mediate circRNA translation in cancer biology. However, the mechanisms by which mA and circRNA in post-transcriptional in HCC progression remain poorly understood. This study aimed to explore the mechanisms by which mA and circRNA in post-transcriptional in HCC progression.

MAIN METHODS

circ_KIAA1429 (hsa_circ_0084922) expression profiles in matched normal and HCC tissues were detected using microarray analysis. The biological roles of circ_KIAA1429 in progression of HCCC were measured both in vitro and in vivo.

KEY FINDINGS

In this study, we found hsa_circ_0084922, which came from KIAA1429, named circ_KIAA1429, was upregulated in HCC cells and tumor tissues. Overexpression of circ_KIAA1429 can facilitate HCC migration, invasion, and EMT process. However, knockdown of circ_KIAA1429 lead to the opposite results. Furthermore, it was demonstrated that Zeb1 was the downstream target of circ_KIAA1429. Up-regulation of Zeb1 led to HCC cells metastasis induced by circ_KIAA1429. In addition, YTHDF3 enhanced Zeb1 mRNA stability via an mA dependent manner.

SIGNIFICANCE

This study revealed that circ_KIAA1429 could accelerate HCC advancement, maintained the expression of Zeb1 through the mechanism of mA-YTHDF3-Zeb1 in HCC. What's more, it might represent a potential therapeutic target in HCC.