State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Center for Translational Medicine, School of Life Sciences, Nanjing University, Nanjing, 210000, China; Department of Urology, University of California, San Francisco, San Francisco, CA, 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, 94158, USA.
State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Center for Translational Medicine, School of Life Sciences, Nanjing University, Nanjing, 210000, China.
Biochem Biophys Res Commun. 2021 Jan 1;534:597-603. doi: 10.1016/j.bbrc.2020.11.034. Epub 2020 Nov 19.
Ubiquitin Conjugating Enzyme E2 C (UBE2C) has a key oncogenic role in many human malignancies, including gastric cancer. However, it remains largely unknow at which level UBE2C expression is altered, as well as what are the downstream targets of UBE2C. In this study, we show that UBE2C is frequently overexpressed in gastric cancer patients. Interestingly, high expression of UBE2C mRNA instead of genome amplification is the predominant alterations observed in both stomach adenocarcinoma. We then confirmed that silencing UBE2C not only suppresses gastric cancer colony formation, but also inhibits DNA biosynthesis. Furthermore, we discovered that microRNA-300 is able to suppress gastric cancer progression through reducing UBE2C mRNA abundance, which is protected by an RNA binding protein HuR. Lastly, through an analysis of genes whose expressions correlate with that of UBE2C from gastric cancer cell lines, we have proposed several key genes that can be regulated by UBE2C, contributing to its oncogenic activity.
泛素连接酶 E2 C（UBE2C）在许多人类恶性肿瘤中具有关键的致癌作用，包括胃癌。然而，UBE2C 的表达在哪个水平上发生改变，以及 UBE2C 的下游靶标是什么，仍然很大程度上未知。在这项研究中，我们表明 UBE2C 在胃癌患者中经常过表达。有趣的是，在胃腺癌中观察到的主要改变是 UBE2C mRNA 的高表达，而不是基因组扩增。然后，我们证实沉默 UBE2C 不仅抑制胃癌集落形成，而且抑制 DNA 生物合成。此外，我们发现 microRNA-300 能够通过降低 UBE2C mRNA 丰度来抑制胃癌的进展，而 HuR 这种 RNA 结合蛋白可以保护其免受抑制。最后，通过对胃癌细胞系中与 UBE2C 表达相关的基因进行分析，我们提出了几个可以被 UBE2C 调控的关键基因，这些基因有助于其致癌活性。
