m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p

Abstract

Background: N6-methyladenosine (m6A) has been validated to play a vital role in human cancers. However, the modulation of m6A modification on renal cell carcinoma (RCC) and long non-coding RNA (lncRNA) LHX1-DT is still unknown. Methods: The m6A levels of RCC tissues and cell lines were detected by colorimetry assay. Differentially expressed lncRNAs and m6A levels were identified by microarray analysis. Functional assays were designed to verify the impacts of lncRNA LHX1-DT (LHX1-DT) on RCC cell proliferation and invasion. The interaction between insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) and LHX1-DT was detected by RNA immunoprecipitation and luciferase reporter assays. Results: LHX1-DT was downregulated in RCC tissues and decreased LHX1-DT expression predicted poor overall survival in RCC patients. Functional experiments uncovered that LHX1-DT overexpression dramatically inhibited cell proliferation and invasion. Mechanistically, METTL14-mediated m6A reader IGF2BP2 could recognize the m6A modification site of LHX1-DT and enhance its stability. LHX1-DT functioned as a competing endogenous RNA (ceRNA) to sponge miR-590-5p, leading to the downregulation of the target programmed cell death factor 4 (PDCD4) to promote RCC cell proliferation and invasion. Conclusions: LHX1-DT is an independent prognostic biomarker for RCC. The IGF2BP2/LHX1-DT/miR-590-5p/PDCD4 axis inhibits the progression and is a novel therapeutic target.