The lncRNA Promotes Hepatocellular Carcinoma Cell Cycle Progression by Regulating the HuR/CDK4 Axis.

Long noncoding RNAs (lncRNAs) represent promising therapeutic targets associated with hepatocellular carcinoma (HCC). lncRNA VPS9D1 antisense RNA 1 () regulates colon and prostate cancer, but its relevance in HCC remains to be clarified. Using microarray data from the NCBI Gene Expression Omnibus (GEO) database (GSE65485) and The Cancer Genome Atlas (TCGA) database, expression in HCC and normal liver tissue sample HCC were compared. Relative lncRNA expression was also measured through real-time quantitative PCR (qPCR) in 80 pairs of HCC tumor and paracancerous tissues and in human HCC cell lines. knockdown was achieved by transfecting these HCC cells with a specific siRNA construct and the proliferation of these cells was quantified through cell proliferation assays and colony formation assays, while flow cytometry was employed to assess their cell cycle progression. The role of the lncRNA as a regulator of HCC tumorigenesis was also assessed by subcutaneously implanting BALB/c nude mice with HepG2 cells stably expressing either sh- or a control shRNA construct. Mechanistic analyses were additionally conducted by examining and expression through western blotting and qPCR. expression was significantly increased in HCC tissues in the analyzed databases and our independent tissue samples. Elevated expression was related to larger tumor size and more advanced tumor, node, metastasis (TNM) stage, and HCC patients expressing higher levels of this lncRNA exhibited poorer survival outcomes. Knocking down impaired the proliferative and colony formation activity of HepG2 cells while promoting their apoptotic death. Consistently, silencing suppressed HCC tumor growth Mechanistically, was able to bind to the HuR protein and thereby influence the stability and expression of the mRNA, thus impacting HCC cell proliferation. The /HuR/CDK4 signaling axis regulates HCC tumor cell oncogenic activity, highlighting this pathway as a promising therapeutic target.