MicroRNA-377-3p promotes cell proliferation and inhibits cell cycle arrest and cell apoptosis in hepatocellular carcinoma by affecting EGR1-mediated p53 activation

Abstract

BackgroundHepatocellular carcinoma (HCC) is an aggressive malignant carcinoma with a high fatality rate. MicroRNAs (miRNAs) have been found to regulate the development of multiple cancers, including HCC. Materials and methodsQuantitative polymerase chain reaction (qPCR) were implemented to evaluate RNA level and western blot to detect protein level. Cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), flow cytometry and in vivo assays were performed to evaluate the biological functions of RNAs on HCC cell proliferation, cell cycle and apoptosis. Luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays were carried out to evaluate the underlying mechanisms. ResultsMiR-377-3p promotes cell proliferation and inhibits cell cycle arrest and cell apoptosis in HCC. MiR-377-3p downregulates transcription factor EGR1 expression to weaken the activation of p53. p53 inhibits CCNB1, CCNB2 and CHEK1 expressions and activates THBS1, IGFBP3 and TRIM22 expressions. p53 knockdown promotes the proliferation and inhibits the cell cycle arrest and apoptosis of HCC cells. ConclusionOur study demonstrated the role and underlying mechanisms of miR-377-3p in HCC. MiR-377-3p facilitates the proliferation and suppresses the cell cycle arrest and apoptosis in HCC by affecting transcription factor EGR1-mediated p53 activation.