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VIII型胶原蛋白α2链(COL8A2)是角膜内皮基底膜的重要组成部分,通过诱导上皮-间质转化促进胶质母细胞瘤细胞的恶性发展。

Collagen type VIII alpha 2 chain (COL8A2), an important component of the basement membrane of the corneal endothelium, facilitates the malignant development of glioblastoma cells via inducing EMT.

作者信息

Cheng Ying-Xin, Xiao Lin, Yang Yan-Li, Liu Xiao-Dong, Zhou Xiu-Rong, Bu Zhen-Fu, Cao Pei-Cheng, Wang Dao-Kui

机构信息

Department of Neurosurgery, Wei Fang People's Hospital, No. 151 Guangwen Street, Weifang, Shandong, 261041, People's Republic of China.

Department of Biochemistry, Weifang Medical University, Weifang, Shandong, 261053, People's Republic of China.

出版信息

J Bioenerg Biomembr. 2021 Feb;53(1):49-59. doi: 10.1007/s10863-020-09865-1. Epub 2021 Jan 6.

Abstract

Glioblastoma (GBM) is one of the most lethal tumor of all human cancers. Due to its poor response to chemotherapy and radiotherapy as well as its high rate of recurrence after treatment, the treatment is still undesired. The identification of potential related genes and bio-markers in the development of GBM could provide some new targets for the treatment of GBM. Our purpose in this study was to evaluate the mission of COL8A2 in GBM. Combined with TCGA, Oncomine databases, CGGA, GEPIA website and qRT-PCR analyses, we found that COL8A2 was up-regulated both in GBM tissues and cells compared to the controls. Moreover, the high COL8A2 expression was associated with the shorter overall survival of patients with GBM. The expression of COL8A2 was also positively correlated with metastasis-associated genes including vimentin, snail, slug, MMP2 and MMP7 according to GEPIA website. Knockdown of COL8A2 could suppress the cell proliferation, cell migration and invasion, whereas the overexpression of COL8A2 significantly expedited these processes. What's more, the outcome of western blot analysis manifested that COL8A2 could induced the expression of vimentin, snail, slug, MMP2 and MMP7. Taken together, COL8A2 activated cell proliferation, cell migration and invasion via raising the relative expression of EMT-related proteins in GBM. Therefore, our investigation suggests the oncogenic role of COL8A2 in GBM and provides a potential application of COL8A2 for GBM therapy.

摘要

胶质母细胞瘤(GBM)是所有人类癌症中最致命的肿瘤之一。由于其对化疗和放疗反应不佳,以及治疗后复发率高,其治疗效果仍不理想。鉴定GBM发生发展过程中的潜在相关基因和生物标志物可为GBM的治疗提供一些新靶点。本研究的目的是评估COL8A2在GBM中的作用。结合TCGA、Oncomine数据库、CGGA、GEPIA网站和qRT-PCR分析,我们发现与对照组相比,COL8A2在GBM组织和细胞中均上调。此外,COL8A2高表达与GBM患者较短的总生存期相关。根据GEPIA网站,COL8A2的表达还与包括波形蛋白、蜗牛蛋白、蛞蝓蛋白、基质金属蛋白酶2(MMP2)和基质金属蛋白酶7(MMP7)在内的转移相关基因呈正相关。敲低COL8A2可抑制细胞增殖、细胞迁移和侵袭,而COL8A2的过表达则显著加速这些过程。此外,蛋白质印迹分析结果表明,COL8A2可诱导波形蛋白、蜗牛蛋白、蛞蝓蛋白、MMP2和MMP7的表达。综上所述,COL8A2通过提高GBM中EMT相关蛋白的相对表达来激活细胞增殖、细胞迁移和侵袭。因此,我们的研究表明COL8A2在GBM中具有致癌作用,并为GBM治疗提供了COL8A2的潜在应用。

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