UBE2O Promotes Hepatocellular Carcinoma Cell Proliferation And Invasion By Regulating The AMPKα2/mTOR Pathway

Objective The ubiquitin-conjugating enzyme(E2)is a critical component of the ubiquitin-proteasome system and regulates hepatocarcinogenesis by controlling protein degradation.Ubiquitin-conjugating enzyme E2 O(UBE2O),a member of the E2 family,functions as an oncogene in human cancers.Nevertheless,the role of UBE2O in hepatocellular carcinoma(HCC)remains unknown yet.Methods1.Through clinical data and bioinformatics analysis,the expression level of UBE2O in hepatocellular carcinoma and its relationship with prognosis were studied.2.We overexpressed and knocked down UBE2O and performed CCK-8 and EdU experiments to confirmed that UBE2O can promote the proliferation of HCC cells.3.We overexpressed and knocked down UBE2O and performed Transwell experiments to confirmed that UBE2O can promote the invasion and migration of HCC cells.4.We knocked down UBE2O and performed immunoprecipitation to confirmed that UBE2O promoted AMPKa2 ubiquitination.5.We knocked down UBE2O and performed RT-QPCR and western blot to confirmed the effects of UBE2O on AMPKa2 and mTOR pathway.6.We knocked down UBE2O and AMPKa2 and performed western blot to confirmed that UBE2O acted on mTOR pathway through AMPK2.7.UBE2O was overexpressed and mTOR inhibitors were used to confirmed that UBE2O promoted the proliferation,invasion and metastasis of HCC cells through the mTOR pathway by CCK-8,EdU and Transwell.Results1.UBE2O is highly expressed in HCC and is associated with poor prognosis.2.UBE2O can promote the proliferation of HCC cells.3.UBE2O can promote the invasion and metastasis of HCC cells.4.UBE2O can promote AMPKα2 ubiquitination and degradation.5.UBE2O can reduce AMPKα2 level and activate mTOR pathway.6.UBE2O activates the mTOR pathway by reducing AMPKα2 levels.7.UBE2O promotes the proliferation,invasion and metastasis of HCC cells through the mTOR pathway.Conclusion UBE2O was highly expressed in HCC and its overexpression conferred to the poor clinical outcomes of patients.UBE2O contributed to the malignant behaviors of HCC cells,including cell proliferation,migration,and invasion,by reducing AMPKα2 stability and activating the mTOR pathway.