UBE2C functions as a potential oncogene by enhancing cell proliferation, migration, invasion, and drug resistance in hepatocellular carcinoma cells
UBE2C functions as a potential oncogene by enhancing cell proliferation, migration, invasion, and drug resistance in hepatocellular carcinoma cells
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UBE2C 通过增强肝细胞癌细胞的增殖、迁移、侵袭和耐药性，发挥潜在癌基因的作用
DOI：
10.1042/bsr20182384
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发表时间：
2019-04-30
影响因子：
4
通讯作者：
Yin, Zhenyu
中科院分区：
文献类型：
--
作者：
Xiong, Yu;Lu, Jing;Yin, Zhenyu
肝细胞癌（HCC）是全球癌症相关死亡的第三大主要原因。最近，有报道称泛素结合酶E2C（UBE2C）在人类癌症中过度表达，并作为一种潜在的癌基因。然而，关于UBE2C在HCC进展中的功能作用知之甚少。在本研究中，对癌症基因组图谱（TCGA）数据集中UBE2C信使核糖核酸（mRNA）表达的分析显示，HCC组织中UBE2C mRNA水平显著升高，且与HCC分级较高相关。HCC中UBE2C mRNA水平升高表明生存概率降低。通过功能缺失实验，我们证明敲低UBE2C表达在体外明显抑制了HCC细胞的增殖、迁移和侵袭。此外，敲低UBE2C的HCC细胞对包括阿霉素（ADR）和5 - 氟尿嘧啶（5 - FU）在内的化疗药物治疗表现出更高的敏感性。沉默UBE2C还提高了HCC细胞对索拉非尼（一种获批用于晚期HCC患者的治疗药物）的敏感性。我们的研究结果有力地表明，UBE2C成为HCC预后的一个标志物，阻断UBE2C可能是HCC治疗的一种新策略。
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been reported to be over-expressed 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.