Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been reported to be overexpressed in human cancers and act as a potential oncogene. However, little is known about the functional roles of UBE2C in HCC progression. In the present study, analysis of UBE2C mRNA expression in The Cancer Genome Atlas (TCGA) dataset reveals that significantly higher UBE2C mRNA levels was found in HCC tissues and associated with higher HCC grade. Elevated UBE2C mRNA levels in HCC indicated worsened survival probabilities. Through performing loss-of-function assays, we demonstrated that knockdown of UBE2C expression obviously suppressed proliferation, migration, and invasion of HCC cells in vitro. Moreover, HCC cells with UBE2C knockdown showed higher sensitivity for the treatment of chemotherapeutic drug, including adriamycin (ADR) and 5-fluorouracil (5-FU). Silencing of UBE2C also increased the sensitivity of HCC cells to sorafenib, an approved treatment for patients with advanced-stage HCC. Our findings strongly suggest that UBE2C emerges as a marker for prognosis in HCC, and blocking UBE2C may be a novel strategy for HCC therapies.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related mortality worldwide [1]
Ubiquitin-conjugating enzyme E2C (UBE2C) is nearly undetectable in normal tissues, at both the mRNA or protein levels, while increasing evidence has shown that UBE2C expression is up-regulated in several human cancers, such as esophageal squamous-cell carcinoma, gastric cancer, and non-small cell lung cancer and rectal cancer [4,5,6,7]
In order to investigate the role of UBE2C in HCC tumorigenesis, we examined the HCC database of The Cancer Genome Atlas (TCGA) to evaluate the differential expression of UBE2C between normal and HCC tissues
Summary
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related mortality worldwide [1]. During the past two decades, the great advancement of HCC treatment has been achieved, including surgical resection, ablation, liver transplantation, and targetted therapy. The 5-year survival rate for HCC has remained unsatisfied at less than 12% due to tumor relapse and metastasis [2,3]. Ubiquitin-conjugating enzyme E2C (UBE2C) is a member of the E2 family and encoded by the UbcH10 gene located on human chromosome 20q13.12, which catalyzes degradation of several target proteins. UBE2C is nearly undetectable in normal tissues, at both the mRNA or protein levels, while increasing evidence has shown that UBE2C expression is up-regulated in several human cancers, such as esophageal squamous-cell carcinoma, gastric cancer, and non-small cell lung cancer and rectal cancer [4,5,6,7]. Its functional role in HCC carcinogenesis remains poorly defined
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