Circnfix Facilitates Hepatocellular Carcinoma Progression By Targeting Mir-3064-5p/Hmga2 To Enhance Glutaminolysis

Hepatocellular carcinoma (HCC) is acknowledged to be a fatal malignant cancer around the world. Circular RNAs (circRNAs) function as crucial regulators in the pathological procession of HCC. Here, we elucidated the biological function of a novel circRNA, circNFIX, in HCC tumorigenesis. qRT-PCR was performed to determine the expressions of circNFIX, miR-3064-5p, and HMGA2. circNFIX stability was evaluated after treatment with ribonuclease R. The growth and invasion of HCC cells were assessed by CCK8 and transwell assays. Protein levels were measured by Western blotting. The levels of glutaminolysis metabolites were evaluated by commercial kits. Dual-luciferase report assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were performed for validating the interaction between miR-3064-5p and circNFIX/HMGA2. Tumor growth in vivo was detected using xenograft assay. Our results showed that circNFIX was remarkably up-regulated in HCC and was associated with a poor survival. Knockdown of circNFIX repressed proliferation, invasion and glutaminolysis of HCC cells. Moreover, circNFIX directly sponged miR-3064-5p to release HMGA2 expression, and thus conferred the malignant development of HCC. In conclusion, circNFIX serves as a competing endogenous RNA to accelerate HCC progression via regulating miR-3064-5p/HMGA2 axis, suggesting a therapeutic strategy for HCC intervention.