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长链非编码RNA EPIC1促进胶质瘤细胞增殖、迁移及耐药性

Long Non-coding RNA EPIC1 Promotes Cell Proliferation and Motility and Drug Resistance in Glioma.

作者信息

Wang Jianjiao, Yang Shuguang, Ji Qiongyu, Li Qingsong, Zhou Fenggang, Li Yang, Yuan Fei, Liu Jie, Tian Yu, Zhao Yan, Zheng Yongri

机构信息

Department of Neurosurgery, the 2nd Affiliated Hospital, Harbin Medical University, Harbin 150086, China.

Huxi Hospital Affiliated to Jining Medical College, Shanxian Central Hospital, Heze 274300, China.

出版信息

Mol Ther Oncolytics. 2020 Mar 30;17:130-137. doi: 10.1016/j.omto.2020.03.011. eCollection 2020 Jun 26.

Abstract

Evidence has revealed that long non-coding RNAs (lncRNAs) are involved in carcinogenesis and tumor progression. lncRNAs play an important role in regulation of numerous cellular processes including cell proliferation, apoptosis, cell cycle, differentiation, and motility. Several studies have demonstrated that lncRNA EPIC1 governs cell growth, cell cycle, migration, invasion, and drug resistance in human malignancies. However, the role of EPIC1 and its underlying molecular mechanisms in glioma have not been investigated. In this study, we determined the function of EPIC1 in glioma cells via upregulation or downregulation of EPIC1. We further dissected the mechanism of EPIC1-mediated tumor progression in glioma. Our results showed that inhibition of EPIC1 suppressed cell viability, induced apoptosis, inhibited cell invasion, and increased cell sensitivity to temozolomide in glioma cells. Consistently, overexpression of EPIC1 exhibited the opposite effects in glioma cells. Moreover, our data suggest that EPIC1 exerts its biological functions via targeting Cdc20 in glioma cells. In line with this, overexpression of Cdc20 reversed the EPIC1-mediated tumor progression in glioma cells. Therefore, targeting EPIC1 might be a useful approach for glioma treatment.

摘要

已有证据表明,长链非编码RNA(lncRNA)参与肿瘤发生和肿瘤进展。lncRNA在调控包括细胞增殖、凋亡、细胞周期、分化和运动性在内的众多细胞过程中发挥重要作用。多项研究表明,lncRNA EPIC1在人类恶性肿瘤中调控细胞生长、细胞周期、迁移、侵袭和耐药性。然而,EPIC1在胶质瘤中的作用及其潜在分子机制尚未得到研究。在本研究中,我们通过上调或下调EPIC1来确定其在胶质瘤细胞中的功能。我们进一步剖析了EPIC1介导的胶质瘤肿瘤进展机制。我们的结果表明,抑制EPIC1可抑制胶质瘤细胞的活力,诱导凋亡,抑制细胞侵袭,并增加细胞对替莫唑胺的敏感性。同样,在胶质瘤细胞中过表达EPIC1则表现出相反的效果。此外,我们的数据表明,EPIC1在胶质瘤细胞中通过靶向Cdc20发挥其生物学功能。与此一致的是,过表达Cdc20可逆转EPIC1介导的胶质瘤细胞肿瘤进展。因此,靶向EPIC1可能是一种治疗胶质瘤的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb85/7163045/aa238e721da6/fx1.jpg

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