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RASAL1的过表达表明卵巢癌预后不良并促进其侵袭。

Overexpression of RASAL1 Indicates Poor Prognosis and Promotes Invasion of Ovarian Cancer.

作者信息

Chang Rui-Xia, Cui Ai-Ling, Dong Lu, Guan Su-Ping, Jiang Ling-Yan, Miao Cong-Xiu

机构信息

Department of gynecology, Heping Hospital affiliated to Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.

Central Laboratory, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.

出版信息

Open Life Sci. 2019 May 21;14:133-140. doi: 10.1515/biol-2019-0015. eCollection 2019 Jan.

Abstract

RAS protein activator like-1 (RASAL1) exists in numerous human tissues and has been commonly demonstrated to act as a tumor suppressor in several cancers. This study aimed to identify the functional characteristics of RASAL1 in ovarian adenocarcinoma and a potential mechanism of action. We analyzed RASAL1 gene expression in ovarian adenocarcinoma samples and normal samples gained from the GEO and Oncomine databases respectively. Then the relationship between RASAL1 expression and overall survival (OS) was assessed using the Kaplan-Meier method. Furthermore, the biological effect of RASAL1 in ovarian adenocarcinoma cell lines was assessed by Quantitative real time-PCR (qRT-PCR), Cell Counting Kit-8 (CCK-8), western blot, wound healing and transwell assay. The statistical analysis showed patients with higher RASAL1 expression correlated with worse OS. The in vitro assays suggested knockdown of RASAL1 could inhibit cell proliferation, cell invasion and migration of ovarian adenocarcinoma. Moreover, the key proteins in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) signaling pathway were also decreased in ovarian adenocarcinoma cells with RASAL1 silencing. These findings provide promising evidence that RASAL1 may be not only a powerful biomarker but also an effective therapeutic target of ovarian adenocarcinoma.

摘要

RAS 蛋白激活剂样 1(RASAL1)存在于多种人体组织中,并且在多种癌症中通常被证明具有肿瘤抑制作用。本研究旨在确定 RASAL1 在卵巢腺癌中的功能特性及其潜在作用机制。我们分别分析了从 GEO 和 Oncomine 数据库获得的卵巢腺癌样本和正常样本中的 RASAL1 基因表达。然后使用 Kaplan-Meier 方法评估 RASAL1 表达与总生存期(OS)之间的关系。此外,通过定量实时聚合酶链反应(qRT-PCR)、细胞计数试剂盒-8(CCK-8)、蛋白质免疫印迹法、伤口愈合实验和 Transwell 实验评估了 RASAL1 在卵巢腺癌细胞系中的生物学效应。统计分析表明,RASAL1 表达较高的患者与较差的总生存期相关。体外实验表明,敲低 RASAL1 可抑制卵巢腺癌的细胞增殖、细胞侵袭和迁移。此外,在 RASAL1 沉默的卵巢腺癌细胞中,丝裂原活化蛋白激酶/细胞外信号调节激酶(MEK/ERK)信号通路中的关键蛋白也减少。这些发现提供了有力证据,表明 RASAL1 不仅可能是一种强大的生物标志物,而且可能是卵巢腺癌的有效治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/423c/7874762/e25fba823090/biol-14-133-g001.jpg

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