LINC00707 impairs the Natural Killer cell antitumour activity in hepatocellular carcinoma through decreasing YTHDF2 stability

Abstract

AbstractHepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer and ranks third in cancer‐related fatalities. The recognized involvement of long noncoding RNAs (lncRNAs) in several cancer types, including HCC, inspired this study to explore a novel lncRNA's functional importance in the progression of HCC. To achieve this, lncRNA microarray analysis was conducted on three distinct sets of HCC tissues, revealing LINC00707 as the most significantly upregulated lncRNA. Further research into its biological functions has revealed that LINC00707 acts as an oncogene, driving HCC progression by enhancing the proliferation, migration and invasion of HCC cells. Mechanistic insights were provided, demonstrating that LINC00707 interacts with YTH N6‐methyladenosine RNA‐binding protein 2 (YTHDF2), thus facilitating the ubiquitination‐dependent degradation of the YTHDF2 protein. Furthermore, LINC00707 was found to influence the cytotoxicity of NK‐92MI cells against HCC cells through its interactions with YTHDF2. These findings significantly contribute to a deeper understanding of the role played by LINC00707 in the progression of HCC.