LINC00486 drives hepatocellular carcinoma progression via stabilization of YAP1 mRNA

Hepatocellular carcinoma (HCC) is a major global health concern due to its high incidence and poor prognosis. Long noncoding RNAs (lncRNAs) have recently emerged as crucial regulators in the intricate landscape of cancer progression, and LINC00486, a newly identified lncRNA, has attracted scientific interest. In this study, we analyze LINC00486 expression in 45 paired HCC and normal tissues, revealing its upregulation in tumors, particularly those with larger size, poor differentiation, and metastasis. Functional experiments including cell counting kit-8‌ assay and flow cytometry reveal that knockdown of LINC00486 significantly suppresses cell proliferation, induces cell cycle arrest at the G2/M phase, and promotes apoptosis in HCC cell lines. Additionally, real-time quantitative PCR and western blotting assays indicate that LINC00486 downregulation suppresses epithelial-mesenchymal transition behavior by up-regulating the expression of E-cadherin and down-regulating the expression of N-cadherin and Vimentin. Mechanistically, LINC00486 stabilizes YAP1 mRNA by facilitating its interaction with the RNA-binding protein ELAVL1. This stabilization activates the YAP1 signaling pathway and subsequently up-regulates the expression of the downstream target CDK6. Overexpressing YAP1 reverses the tumor-inhibitory effects of LINC00486 knockdown in vitro and in vivo. Our findings suggest that LINC00486 promotes HCC progression by enhancing YAP1 stability, providing a novel perspective on the molecular mechanisms underlying HCC development and potential new diagnostic markers and therapeutic targets.