The long noncoding RNA cardiac hypertrophy-related factor plays oncogenic roles in hepatocellular carcinoma by downregulating microRNA-211

Abstract

Background: Hepatocellular carcinoma (HCC) is the most major type of primary hepatic cancer. This study aimed to explore the possible oncogenic effects of the long noncoding RNA cardiac hypertrophy–related factor (CHRF) on HCC, as well as the underlying possible mechanism. Methods: The expression levels of CHRF and microRNA-211 (miR-211) in HCC tissues and/or cell lines HepG2 and Huh-7 were measured using quantitative reverse transcription polymerase chain reaction. Cell transfection was conducted to change the expression levels of CHRF and miR-211 in cells. Cell viability and apoptosis were assessed using the cell counting kit-8 assay and annexin V-phycoerythrin staining, respectively. The pull-down assay and RNA immunoprecipitation were performed to analyze the association between CHRF and miR-211. The expression of the key factors involving in cell proliferation, cell apoptosis, and epithelial-mesenchymal transition (EMT) process, as well as the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin pathways, were evaluated by Western blot analysis. Results: CHRF was highly expressed in HCC tissues and positively associated with the TNM stage, differentiation, and size of tumors. Overexpression of CHRF promoted HepG2 cell viability, proliferation, and EMT process. CHRF knockdown had opposite effects. Moreover, CHRF negatively regulated the expression of miR-21, and miR-21 was a direct target of CHRF. Overexpression of miR-211 reversed the effects of CHRF on HepG2 and Huh-7 cell viability, proliferation, and EMT process. Furthermore, overexpression of CHRF activated the PI3K/AKT and Wnt/β-catenin pathways in HepG2 cells by downregulating miR-211. Conclusion: CHRF played oncogenic roles in HCC. The overexpression of CHRF promoted HepG2 and Huh-7 cell viability, proliferation, and EMT process by downregulating miR-211 and then activating the PI3K/AKT and Wnt/β-catenin pathways.