RNF216P1 functions as an oncogenic gene through modulating miR-195-5p/ATG4B axis in hepatocellular carcinoma.

Recent studies have highlighted the critical roles of long non-coding RNAs (lncRNAs) in tumorigenesis and progression. Here, we report that the lncRNA RNF216P1 is significantly upregulated in hepatocellular carcinoma (HCC) and contributes to tumor growth. To elucidate its underlying mechanisms, we first analyzed the transcriptional levels of RNF216P1 and its targets, miR-195-5p and autophagy related 4B cysteine peptidase (ATG4B), in HCC tissues using The Cancer Genome Atlas dataset, followed by validation with RT-qPCR. ATG4B protein levels were assessed by Western blotting. Functional assays-including xenograft models, CCK-8 viability tests, wound-healing assays, and Transwell migration assays-were performed to evaluate the role of RNF216P1 in HCC progression. Furthermore, the interactions between RNF216P1 and miR-195-5p, as well as between miR-195-5p and ATG4B, were confirmed by fluorescence in situ hybridization (FISH), RNA immunoprecipitation assays, and dual-luciferase reporter assays. Collectively, our findings demonstrate that RNF216P1 promotes malignant progression in HCC cells by acting as a competing endogenous RNA for miR-195-5p, thereby upregulating ATG4B and enhancing autophagy. This study identifies a novel ceRNA axis-RNF216P1/miR-195-5p/ATG4B-that plays a pivotal role in HCC development and may represent a potential therapeutic target.