Downregulation of lncRNA OGFRP1 inhibits hepatocellular carcinoma progression by AKT/mTOR and Wnt/β-catenin signaling pathways

摘要

Introduction: Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) by regulating gene expression. However, the identification of functional lncRNAs in HCC remains insufficient. Our study aimed to investigate the function of lncRNA OGFRP1, which has not been functionally researched before, in Hep3B and HepG2 cells. Methods: lncRNA OGFRP1 in HCC cells was down-regulated by using RNAi technology. Quantitative real-time polymerase chain reaction was used to determine the mRNA expression of lncRNA OGFRP1. Cell proliferation was examined by CCK8 and clone formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion were assessed by using Scratch assay and transwell assay, respectively. Protein expression of signaling pathways was determined by using Western blot. Results: Cell proliferation of Hep3B was significantly inhibited by down-regulation of lncRNA OGFRP1 ( P <0.05). Moreover, siOGFRP1 transfection induced Hep3B cell cycle arrest and apoptosis by regulating the expression of related proteins. Cell migration and invasion of Hep3B were also significantly inhibited by down-regulation of lncRNA OGFRP1. Wnt/β-catenin signaling pathway, involved in epithelial–mesenchymal transition (EMT), was inactivated by lncRNA OGFRP1 downregulation, including decreased expression of Wnt3a, β-catenin, N-cadherin and vimentin and increased expression of E-cadherin. We also found that the inhibitory effect of lncRNA OGFRP1 knockdown on Hep3B was mediated by the AKT/mTOR signaling pathway and IGF-1, an AKT signaling activator, could rescue the cellular phenotype. However, knockdown of lncRNA OGFRP1 did not influence cell proliferation, migration and invasion in HepG2 cells. Conclusion: We found that downregulation of lncRNA OGFRP1 suppressed the proliferation and EMT of HCC Hep3B cells through AKT and Wnt/β-catenin signaling pathways. However, lncRNA OGFRP1 exhibited a differentiated function in different HCC cell lines, which required further study in the future.