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微小RNA-140通过直接靶向解聚素金属蛋白酶9抑制胶质瘤的生长和转移。

MicroRNA-140 represses glioma growth and metastasis by directly targeting ADAM9.

作者信息

Liu Xiaogang, Wang Shanjun, Yuan Aiqin, Yuan Xunhui, Liu Bing

机构信息

Department of Neurosurgery, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China.

Department of Neurosurgery, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261030, P.R. China.

出版信息

Oncol Rep. 2016 Oct;36(4):2329-38. doi: 10.3892/or.2016.5007. Epub 2016 Aug 8.

Abstract

Glioma is the most frequent primary malignant tumor of the human brain. Recently, great progress has been made in the combined therapy of glioma. However, the clinical effects of these treatments and prognosis for patients with glioma remains poor. MicroRNAs (miRNAs) have been demonstrated to play important roles in the initiation and progression of various types of human cancers, also including glioma. The present study investigated the expression patterns of microRNA‑140 (miR-140) in glioma, and the roles of miR-140 in glioma cell proliferation, migration and invasion. The results showed that miR-140 was significantly downreuglated in glioma tissues and cell lines, and low expression levels of miR-140 were correlated with World Health Organization (WHO) grade and Karnofsky performance score (KPS) of glioma patients. Restoration of miR-140 obviously suppressed glioma cell proliferation, migration and invasion. In addition, a disintegrin and metalloproteinase 9 (ADAM9) was identified as a novel direct target gene of miR-140 in glioma. Furthermore, knockdown of ADAM9 simulated the tumor suppressor functions of miR-140, while overexpression of ADAM9 abrogated these suppressive effects induced by miR-140 in glioma cells. In conclusion, the present study demonstrated the expression and clinical roles of miR-140 in glioma and suggested that miR-140 inhibited proliferation, migration and invasion of glioma cells, partially at least via suppressing ADAM9 expression. Therefore, miR-140 may be a novel candidate target for the development of therapeutic strategies for patients with glioma.

摘要

神经胶质瘤是人类大脑中最常见的原发性恶性肿瘤。近年来,神经胶质瘤的联合治疗取得了很大进展。然而,这些治疗方法的临床效果以及神经胶质瘤患者的预后仍然较差。微小RNA(miRNA)已被证明在包括神经胶质瘤在内的各种人类癌症的发生和发展中发挥重要作用。本研究调查了微小RNA-140(miR-140)在神经胶质瘤中的表达模式,以及miR-140在神经胶质瘤细胞增殖、迁移和侵袭中的作用。结果显示,miR-140在神经胶质瘤组织和细胞系中显著下调,且miR-140的低表达水平与神经胶质瘤患者的世界卫生组织(WHO)分级和卡诺夫斯基功能状态评分(KPS)相关。miR-140的恢复明显抑制了神经胶质瘤细胞的增殖、迁移和侵袭。此外,一种解整合素和金属蛋白酶9(ADAM9)被确定为神经胶质瘤中miR-140的一个新的直接靶基因。此外,敲低ADAM9模拟了miR-140的肿瘤抑制功能,而ADAM9的过表达消除了miR-140在神经胶质瘤细胞中诱导的这些抑制作用。总之,本研究证明了miR-140在神经胶质瘤中的表达及临床作用,并表明miR-140至少部分通过抑制ADAM9的表达来抑制神经胶质瘤细胞的增殖、迁移和侵袭。因此,miR-140可能是神经胶质瘤患者治疗策略开发的一个新的候选靶点。

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