PABPC1 interacts with AGO2 and is responsible for the microRNA mediated gene silencing in high grade hepatocellular carcinoma

Abstract

MicroRNAs (miRNA) have been considered as oncogenes, tumor suppressors, or modulators involved in the tumorigenesis and metastasis of hepatocellular carcinoma (HCC) today. As miRNA induces mRNA degradation or translation inhibition in RNA-induced silencing complex (RISC), the changes in RISC and its interacted proteins might contribute to the functional alternations of miRNA. To explore the molecular function of RISC in HCC, we co-purified RISC interacted proteins by anti-AGO2 antibody and identified 12 AGO2 binding proteins by mass spectrometry. Among them, we found PABPC1 was over-expressed in HCC, especially in high grade HCC. Further studies showed PABPC1 interacted with AGO2 in the cytoplasm of HCC cells. This interaction increased the recruitment of mRNA to RISC and enhanced the inhibition efficiency of miRNA. In general, PABPC1 acted as an oncogene in HCC as it induced cell proliferation by promoting entry into the S phase and enhanced the anchorage independent growth. Our study identified a novel method by which the activities of miRNA could be enhanced with the increase of PABPC1 in HCC and could explain why several miRNAs play critical roles in HCC progression without clear level changes. This finding would benefit the diagnosis and treatment of HCC.