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

Abstract

Ferroptosis has important value in cancer treatment. It is significant to explore thenew ferroptosis-related lncRNAs(FRLs) prediction model in Hepatocellular carcinoma(HCC) and the potential molecular mechanism of ferroptosis-related lncRNAs. Weconstructed a prognostic multi-lncRNA signature based on ferroptosis-relateddifferentially expressed lncRNAs in HCC. qRT-PCR was applied to determine theexpression of lncRNA in HCC cells. The biological roles of NRAV in vitro and in vivowere determined by performing a series of functional experiments. Further, dualluciferasereporter and RNA immunoprecipitation (RIP) assays were used to confirm theinteraction of NRAV with miR-375-3P. We identified 6 differently expressed lncRNAsassociated with the prognosis of HCC. Kaplan-Meier analyses revealed the high-risklncRNAs signature associated with poor prognosis of HCC. Moreover, the AUC of thelncRNAs signature showed the utility in predicting HCC prognosis. Further functionalexperiments show that the high expression of NRAV can strengthen the viciousness ofHCC. Interestingly, we found that NRAV can enhance iron export and ferroptosisresistance. Further research showed NRAV via competitively binds to miR-375-3P andattenuates the inhibitory effect of miR-375-3P on SLC7A11, affecting the prognosis ofpatients with HCC. In conclusion, We developed a novel FRLs prognostic model withimportant predictive value for the prognosis of hepatocellular carcinoma. NRAV plays animportant role in ferroptosis induction through the miR-375-3P/SLC7A11 axis.