Long non-coding RNA CASC2 suppresses malignancy in human gliomas by miR-21
Long non-coding RNA CASC2 suppresses malignancy in human gliomas by miR-21
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长非编码RNA CASC2通过miR-21抑制人胶质瘤的恶性肿瘤
DOI：
10.1016/j.cellsig.2014.11.011
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发表时间：
2015-02-01
影响因子：
4.8
通讯作者：
Xue, Yi-xue
中科院分区：
文献类型：
--
作者：
Wang, Ping;Liu, Yun-hui;Xue, Yi-xue
长非编码RNA(IncRNAs)在包括癌症在内的许多疾病中都有异常表达。LncRNA CASC2(癌症易感候选基因2)在子宫内膜癌和结直肠癌中被认为是一种肿瘤抑制因子。然而，CASC2在人脑胶质瘤中的作用和功能仍不清楚。在这项研究中，我们证实了CASC2在胶质瘤组织以及U251和087胶质瘤细胞系中低表达。CASC2的过表达抑制了胶质瘤细胞的恶性，包括增殖、迁移和侵袭，并促进了细胞的凋亡。MicroRNA-21(miR-21)在人脑胶质瘤组织和细胞系中过表达，与脑胶质瘤的恶性进展有关。我们发现，上调的CASC2显著降低了miR-21的表达，并且CASC2和miR-21之间存在相互抑制，这是一种Argavite2依赖的方式。此外，生物信息学、荧光素酶报告分析和下拉实验证实miR-21以序列特异性的方式与CASC2结合。MiR-21的引入在很大程度上取消了CASC2介导的抑制胶质瘤细胞增殖、迁移和侵袭以及促进细胞凋亡的作用。本研究表明，CASC2可能通过对miR-21的负性调节而在脑胶质瘤中发挥抑瘤作用，有望成为治疗脑胶质瘤的新靶点。(C)2014 Elsevier Inc.保留所有权利。
Long non-coding RNAs (IncRNAs) are aberrantly expressed in many diseases including cancer. LncRNA CASC2 (cancer susceptibility candidate 2) has been characterized as a tumor suppressor in endometrial cancer and colorectal cancer. However, the role and function of CASC2 in human gliomas remain unknown. In this study, we confirmed that CASC2 was lowly expressed in glioma tissues as well as in U251 and 087 glioma cell lines. Overexpression of CASC2 inhibited the malignancy of glioma cells, including proliferation, migration, and invasion, and promoted cell apoptosis. MicroRNA-21 (miR-21) has been reported to be overexpressed in human glioma tissues and cell lines, which is responsible for the malignant progression of glioma. We found that up-regulated CASC2 decreased the expression of miR-21 significantly and there is a reciprocal repression between CASC2 and miR-21 in an Argonaute2-dependent manner. Furthermore, bioinformatics, luciferase reporter assays and pull-down assay confirmed that miR-21 binds to CASC2 in a sequence-specific manner. Introduction of miR-21 largely abrogated CASC2-mediated inhibition of glioma cell proliferation, migration, and invasion, and promotion of cell apoptosis. This study demonstrated that CASC2 plays a tumor suppressive role in glioma via negative regulation of miR-21, which may be a novel therapeutic target for treating gliomas. (C) 2014 Elsevier Inc. All rights reserved.