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下调DLGAP5可抑制卵巢癌细胞增殖,诱导G/M期阻滞及凋亡。

Knockdown of DLGAP5 suppresses cell proliferation, induces G/M phase arrest and apoptosis in ovarian cancer.

作者信息

Zhang Huijun, Liu Yuan, Tang Shengchun, Qin Xiaomin, Li Lin, Zhou Jinting, Zhang Jing, Liu Bo

机构信息

Department of Obstetrics and Gynecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei 441000, P.R. China.

Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei 441000, P.R. China.

出版信息

Exp Ther Med. 2021 Nov;22(5):1245. doi: 10.3892/etm.2021.10680. Epub 2021 Sep 2.

DOI:10.3892/etm.2021.10680
PMID:34539841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8438692/
Abstract

Discs large-associated protein 5 (DLGAP5) is a microtubule-associated protein and is reported to exert oncogenic role in tumorigenesis, including lung cancer and hepatocellular carcinoma. However, the prognostic value and biological function of DLGAP5 in ovarian cancer (OC) still remain unclear. The present study investigated the expression pattern of DLGAP5 by searching the Oncomine microarray database. The correlation between DLGAP5 and survival prognosis of OC patients was analyzed by the online tool KM-plotter. Knockdown of DLGAP5 was achieved by transfection with small interfering RNA targeting DLGAP5 in two OC cell lines (SKOV3 and CAOV3). Cell proliferation was assessed by Cell Counting Kit-8 assay and colony-formation assay. Flow cytometry was utilized to determine the effects of DLGAP5 on cell cycle distribution and apoptosis. The present study data showed that DLGAP5 was significantly upregulated in OC and its higher expression was associated with poor survival prognosis. Knockdown of DLGAP5 significantly suppressed cell proliferation, induced cell cycle G/M phase arrest and apoptosis. Western blot analysis further demonstrated that DLGAP5 knockdown downregulated the expression of CDK1, Cyclin B1 and Bcl-2, but upregulated Bax expression. Collectively, these data demonstrate that DLGAP5 might be a promising prognostic therapeutic target for OC treatment.

摘要

盘状大蛋白相关蛋白5(DLGAP5)是一种微管相关蛋白,据报道在肿瘤发生过程中发挥致癌作用,包括肺癌和肝细胞癌。然而,DLGAP5在卵巢癌(OC)中的预后价值和生物学功能仍不清楚。本研究通过搜索Oncomine微阵列数据库来研究DLGAP5的表达模式。通过在线工具KM-plotter分析DLGAP5与OC患者生存预后之间的相关性。通过用靶向DLGAP5的小干扰RNA转染两种OC细胞系(SKOV3和CAOV3)来实现DLGAP5的敲低。通过细胞计数试剂盒-8测定法和集落形成测定法评估细胞增殖。利用流式细胞术确定DLGAP5对细胞周期分布和凋亡的影响。本研究数据表明,DLGAP5在OC中显著上调,其高表达与不良生存预后相关。敲低DLGAP5显著抑制细胞增殖,诱导细胞周期G/M期阻滞和凋亡。蛋白质印迹分析进一步证明,敲低DLGAP5可下调CDK1、细胞周期蛋白B1和Bcl-2的表达,但上调Bax表达。总体而言,这些数据表明DLGAP5可能是OC治疗中一个有前景的预后治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/ddc27fb62c9b/etm-22-05-10680-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/fb6f52d2ca3e/etm-22-05-10680-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/100f71aee4ba/etm-22-05-10680-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/604dadf9820c/etm-22-05-10680-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/47dcaf123605/etm-22-05-10680-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/ddc27fb62c9b/etm-22-05-10680-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/fb6f52d2ca3e/etm-22-05-10680-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/100f71aee4ba/etm-22-05-10680-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/604dadf9820c/etm-22-05-10680-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/47dcaf123605/etm-22-05-10680-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/8438692/ddc27fb62c9b/etm-22-05-10680-g04.jpg

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