MiR-144-3p-mediated dysregulation of EIF4G2 contributes to the development of Hepatocellular Carcinoma through ERK pathway
Abstract Background Hepatocellular carcinoma (HCC) is one of the most common cancers with high incidence and mortality. But the underlying mechanisms of HCC still remain unclear. Eukaryotic translation initiation factors (eIFs), showing a large effect on tumor development. In this study, we were aimed to investigate the role of eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) in HCC. Methods Western blot (WB) in 30 paired HCC tissues and tissue microarrays (TMAs) by immunohistochemistry (IHC) in 89 paired HCC samples were performed to assess EIF4G2 expression. Clone formation, Real-Time Cell Analysis (RTCA), wounding-healing and transwell assays were adopted to evaluate the role of EIF4G2 on HCC cell proliferation, migration and invasion ability. The function of EIF4G2 on HCC tumor growth was conducted by xenograft nude mouse model in vivo. The regulation of miR-144-3p on EIF4G2 was performed by luciferase reporter assay and WB. Results EIF4G2 was obviously upregulated in HCC tissues, and high-expression of EIF4G2 was closely related to HCC prognosis. EIF4G2 silencing could inhibit HCC cells growth and metastasis in vitro, and suppress tumorigenesis in vivo by repressing ERK signaling pathway. The results of luciferase reporter assay, WB and IHC staining verified that EIF4G2 was negatively regulated by miR-144. And re-expression of EIF4G2 could partially reverse the inhibiting effect of miR-144 in HCC. Conclusion In summary, our study revealed the role of EIF4G2 in HCC development by activating ERK pathway. We also found that EIF4G2 could be negatively regulated by tumor suppressor miR-144. Our investigations indicated that EIF4G2 might be a promising therapeutic target in HCC.