Ferroptosis-related lncRNA NRAV affects the prognosis of hepatocellular carcinoma via miR-375-3P/SLC7A11 axis

Abstract

Ferroptosis has essential value in cancer treatment. It is significant to explore the new ferroptosis-related lncRNAs(FRLs) prediction model in Hepatocellular carcinoma (HCC) and the potential molecular mechanism of ferroptosis-related lncRNAs. Using differentially expressed lncRNAs associated with ferroptosis, we developed A multi-lncRNA prognostic signature in HCC. We used qRT-PCR to detect lncRNA in HCC cells. We performed functional experiments in vitro and in vivo to determine the biological role of NRAV. Interaction between NRAV and miR-375-3P was confirmed by RNA immunoprecipitation (RIP) assay and dual luciferase reporter. We observe 6 differentially expressed lncRNAs related to the progression of HCC. According to Kaplan-Meier analyses, HCC with a high-risk lncRNAs signature has a poor prognosis. In addition, AUC values confirmed the utility of lncRNAs signature for predicting HCC prognosis. Further functional experiments show that the high expression of NRAV can strengthen the viciousness of HCC. Interestingly, we found that NRAV can enhance iron export and ferroptosis resistance. Further studies showed that NRAV attenuated the inhibition of SLC7A11 by miR-375-3P through competitive binding to miR-375-3P, influencing the prognosis of HCC patients. In conclusion, We developed a novel FRLs prognostic model with crucial predictive value for the prediction of hepatocellular carcinoma. NRAV is essential in ferroptosis induction through the miR-375-3P/SLC7A11 axis.