KIAA1429 promotes non-small-cell lung cancer cell proliferation through the TRERNA1/HOXA6 axis.

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. This study aimed to investigate the mechanism of vir-like m6A methyltransferase-associated protein (VIRMA, also called KIAA1429) in NSCLC cell proliferation. Levels of KIAA1429, long-chain non-coding RNAs translation regulatory long non-coding RNA 1 (lncRNA TRERNA1), and homeobox A6 (HOXA6) were measured in NSCLC cells and normal cells. The enrichment of KIAA1429 and m6A on lncRNA TRERNA1 was detected. LncRNA TRERNA1 stability and subcellular localization of lncRNA TRERNA1 were detected. The binding of EZH2 to lncRNA TRERNA1 was analyzed. The enrichment of EZH2 and H3K27me3 on the HOXA6 promoter was analyzed. The mechanism of KIAA1429 was validated in vivo. KIAA1429 and lncRNA TRERNA1 were overexpressed in NSCLC cells and HOXA6 was downregulated. Knockdown of KIAA1429 significantly reduced NSCLC cell proliferation. KIAA1429 enhanced lncRNA TRERNA1 RNA stability via m6A modification and upregulated lncRNA TRERNA1 expression, which recruited EZH2 and increased H3K27me3 modification in the HOXA6 promoter region, thus suppressing HOXA6 expression. LncRNA TRERNA1 overexpression or HOXA6 downregulation alleviated the inhibitory effect of KIAA1429 downregulation on NSCLC cell proliferation. KIAA1429 downregulation inhibited NSCLC cell proliferation in vivo. In conclusion, KIAA1429 promotes NSCLC proliferation through the TRERNA1/HOXA6 axis.