Li Guoxiong, Lu Anqian, Chen Anna, Geng Shuang, Xu Yu, Chen Xin, Yang Jin
Department of Gastroenterology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
Department of Translational Medicine Center, Affiliated Hospital of Hangzhou Normal University, Institute of Hepatology and Metabolic Diseases of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
J Cancer. 2021 Jun 22;12(17):5125-5135. doi: 10.7150/jca.53282. eCollection 2021.
Basic leucine zipper and W2 domain 2 (BZW2), also known as 5MP1, is a protein related to translation regulation. Evidence from previous studies indicates that BZW2 is involved in tumorigenesis in several cancers. However, little is known about the role of BZW2 in hepatocellular carcinoma (HCC). In this study, we first analyzed the gene expression profile of BZW2 in multiple HCC datasets. Next, we explored the biological effects of BZW2 in HCC cell lines. BZW2 was overexpressed in different HCC cohorts. Multivariate analysis confirmed that increased BZW2 expression is an independent prognostic indicator of shorter overall survival. BZW2 coexpressed genes were mainly enriched in the biological processes of ribonucleoprotein complex biogenesis, rRNA metabolism, translational initiation, and negative regulation of metabolic processes. BZW2 depletion reduced proliferation, clonality, and invasion and increased apoptosis in MHCC97-H cells. Furthermore, BZW2 overexpression or knockdown enhanced or impaired c-Myc expression, respectively. Overall, these findings identified BZW2 as a biomarker of HCC and provided novel insight that the effect of BZW2 on the translatome is a potential mechanism that promotes HCC progression via the c-Myc pathway.
碱性亮氨酸拉链和W2结构域2(BZW2),也被称为5MP1,是一种与翻译调控相关的蛋白质。先前研究的证据表明,BZW2参与多种癌症的肿瘤发生过程。然而,关于BZW2在肝细胞癌(HCC)中的作用知之甚少。在本研究中,我们首先分析了多个HCC数据集中BZW2的基因表达谱。接下来,我们探讨了BZW2在HCC细胞系中的生物学效应。BZW2在不同的HCC队列中过表达。多变量分析证实,BZW2表达增加是总生存期较短的独立预后指标。BZW2共表达基因主要富集于核糖核蛋白复合体生物发生、rRNA代谢、翻译起始以及代谢过程的负调控等生物学过程。BZW2缺失降低了MHCC97-H细胞的增殖、克隆形成能力和侵袭能力,并增加了细胞凋亡。此外,BZW2过表达或敲低分别增强或削弱了c-Myc的表达。总体而言,这些发现确定BZW2为HCC的一个生物标志物,并提供了新的见解,即BZW2对转录组的影响是通过c-Myc途径促进HCC进展的潜在机制。