LncRNA GAS5 Restrains Hepatocellular Carcinoma by Targeting the miR-18a-5p-CADM2 Axis

Long non-coding RNAs (lncRNAs) are key regulators in hepatocellular carcinoma (HCC) progression, yet the function of lncRNA GAS5 in HCC remains controversial. GAS5 expression was analyzed across multiple public datasets. Overexpression experiments were performed in HCC cells to evaluate GAS5's biological role. Bioinformatic prediction, luciferase reporter experiments, and rescue assays were used to elucidate the molecular mechanism. Xenograft mice were established to confirm GAS5's in vivo effects. GAS5 levels were markedly reduced in HCC tissues. Excessive GAS5 suppressed cell viability and colony formation, induced G0/G1 arrest, promoted apoptosis, and inhibited migration and invasion. Mechanistically, GAS5 functioned as a competing endogenous RNA to inhibit miR-18a-5p and restore the expression of the tumor suppressor CADM2. The direct interactions between GAS5 and miR-18a-5p, and between miR-18a-5p and the CADM2 3'-UTR, were validated by luciferase assays. Rescue assays demonstrated that miR-18a-5p overexpression or CADM2 silencing reversed the tumor-suppressive effects of GAS5. In the xenograft mice, excessive GAS5 significantly impaired tumorigenesis and modulated apoptosis- and EMT-related markers. GAS5 suppresses HCC by modulating the miR-18a-5p-CADM2 axis. Our findings offer a new perspective into HCC tumorigenesis and suggest that GAS5 and its downstream network may serve as potential therapeutic targets.