The Expression And Functional Roles Of Oncogene UBE2C In Hepatocellular Carcinoma Cells

BackgroundHepatocellular carcinoma(HCC)is the third crucial cause of cancer-related mortality across the globe.Menawhile,the symptoms of HCC is not obvious and it often progresses to an advanced stage rapidly.These characteristics raise the difficulty for the treatment of liver cancer.Despite the rapid development of diagnosis and treatment of liver cancer in recent years,the overall prognosis of patients is still not optimistic.Nowadays,several reports have suggested that ubiquitin-conjugated enzyme E2C(UBE2C)is overexpressed in human cancers and acts as a potential oncogene.However,little is known about the functional role of UBE2C in the development and progression of hepatocellffar carcinoma.MethodsIn this study,the bioinformatics method was used to analyze the correlation between UBE2C inRNA expression and tumor grade or prognosis.Immunohistochemistry and RT-PCR were used to confirm the results in clinical specimens and analyze the associations between UBE2C mRNA expression and clinicopathological parameters.In additon,we established HCC cell lines SK-Hep-1 and SMMC-7721 that stably down-regulated UBE2C in order to explore the bio-function by CCK-8,clone-formation and transwell assay.Moreover,we used two common chemotherapy drugs adriamycin(ADR),5-fluorouracil(5-fu)and molecular targeted agent sorafenib to treat the control group and the group with UBE2C knockdown,and tested the effect of UBE2C on the drug sensitivity of liver cancer cells through CCK-8 assay.ResultsThe results showed that in the TGA database,the level of UBE2C mRNA in liver cancer tissues was significantly higher than that in normal tissues,which was positively correlated with the classification of liver cancer,and the clinical prognosis of patients with high expression of UBE2C mRNA was remarkable worse.RT-PCR and immunohistochemistry results of Clinical specimens also verify the UBE2C expression in liver cancer tissue was significantly higher than tissue adjacent to carcinoma,and the expression of UBE2C was related to cancer differentiation degree(p=0.0202).metastasis(p=0.0298)and recurrence(overall p=0.0020,short-term p=0.0298)in patients,Kaplan Meier survival analysis showed that there was close correlation between the expression of UBE2C.patients' overall survival time(p=0.0131)and tumor-free survival time(p= 0.0004).Cell function experiments showed that interfering UBE2C expression could inhibit the proliferation,migration and invasion in liver cancer cells.Finally,we found that knockdown of UBE2C can increase the sensitivity of hepatocellular carcinoma cells to adriamycin,5-fluorouracil and molecular targeted agent sorafenib.ConclusionOur conclusion was that UBE2C is upregulated in liver cancer tissues and was closely related to various malignant clinicopathological features and poor prognosis of patients,indicating that UBE2C had the potential to be used as a prognostic marker for liver cancer.Knockdown of UBE2C could inhibit the proliferation,invasion and migration of HCC cells,and improved the sensitivity of HCC cells to the chemotherapy drugs adriamycin,5-fluorouracil and targeted agent sorafenib,suggesting that UBE2C played an important role in the occurrence,development and drug resistance of HCC,and blocking UBE2C might be a new strategy for the treatment of HCC.