UBE2C mRNA expression controlled by miR-300 and HuR determines its oncogenic role in gastric cancer
UBE2C mRNA expression controlled by miR-300 and HuR determines its oncogenic role in gastric cancer
复制标题
由 miR-300 和 HuR 控制的 UBE2C mRNA 表达决定了其在胃癌中的致癌作用。
DOI：
10.1016/j.bbrc.2020.11.034
复制
发表时间：
2021-01-01
影响因子：
3.1
通讯作者：
Zhao, Quan
中科院分区：
文献类型：
--
作者：
Wang, Ying;Huang, Feifei;Zhao, Quan
泛素结合酶E2 C(UBE2C)在包括胃癌在内的许多人类恶性肿瘤中起着关键的致癌作用。然而，它在很大程度上仍然不知道UBE2C的表达在哪个水平上被改变，以及UBE2C的下游靶标是什么。在这项研究中，我们发现UBE2C在胃癌患者中经常过表达。有趣的是，在两种胃腺癌中观察到的主要变化是UBE2C mRNA的高表达而不是基因组扩增。我们随后证实，沉默UBE2C不仅可以抑制胃癌克隆的形成，还可以抑制DNA的生物合成。此外，我们发现microRNA-300能够通过减少受RNA结合蛋白Hur保护的UBE2C mRNA丰度来抑制胃癌的进展。最后，通过对胃癌细胞系中与UBE2C表达相关的基因的分析，我们提出了UBE2C调控的几个关键基因，这些基因与UBE2C的致癌活性有关。(C)2020 Elsevier Inc.保留所有权利。
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. (C) 2020 Elsevier Inc. All rights reserved.