Effects of Long Form of CAPON Overexpression on Glioma Cell Proliferation are Dependent on AKT/mTOR/P53 Signaling
Effects of Long Form of CAPON Overexpression on Glioma Cell Proliferation are Dependent on AKT/mTOR/P53 Signaling
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长形式 CAPON 过表达对神经胶质瘤细胞增殖的影响取决于 AKT/mTOR/P53 信号传导
DOI：
10.7150/ijms.31579
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发表时间：
2019-04
影响因子：
3.6
通讯作者：
Gao Shangfeng
中科院分区：
文献类型：
--
作者：
Liang Dong;Song Yunnong;Fan Guangwei;Ji Daofei;Zhang Tong;Nie Er;Liu Xuejiao;Liang Jun;Yu Rutong;Gao Shangfeng
背景：CAPON在人脑中有两种亚型：长型CAPON（CAPON-L）和短型CAPON（CAPON-S）。最近的研究表明CAPON参与肿瘤细胞的生长。本研究旨在揭示CAPON两种亚型在胶质瘤细胞增殖中的作用。材料和方法：在U87和U251胶质瘤细胞中建立慢病毒介导的CAPON-L或CAPON-S过表达的稳定细胞系。细胞计数试剂盒-8和集落形成试验用于评估细胞增殖。Western blot分析细胞周期相关蛋白，流式细胞术分析细胞周期进程。AKT/mTOR通路和P53的一些重要分子也通过Western印迹分析进行测量。结果：CAPON-L过表达对U251细胞有明显的抑制作用，对U87细胞有明显的促进作用。CAPON-L过表达可抑制U251细胞周期进程，下调U87细胞Cyclin D1、CDK 4和CDK 6的表达，上调U87细胞CDK 6的表达。CAPON-L过表达可显著降低U251细胞中AKT、mTOR和S6的磷酸化水平和/或总水平，而对U87细胞中这些信号分子无影响，但AKT在Thr-308位点的磷酸化水平显著升高。在CAPON-L过表达的U251细胞中，转染组成型活性AKT（myr-AKT）部分逆转了AKT和S6磷酸化的降低。此外，我们发现在CAPON-L过表达的U87细胞中野生型P53水平显著降低。CAPON-S的过表达还抑制了U251细胞的增殖，阻断了细胞周期进程，并降低了U251细胞中AKT/mTOR通路的活性。结论：CAPON-L过表达对胶质瘤细胞增殖的影响依赖于AKT/mTOR/P53活性。CAPON过表达通过AKT/mTOR信号通路抑制U251细胞增殖，CAPON-L过表达通过下调P53表达促进U87细胞增殖。
Background: CAPON has two isoforms in human brain: long form of CAPON (CAPON-L) and short form of CAPON (CAPON-S). Recent studies have indicated the involvement of CAPON in tumor cell growth. We aimed to reveal the role of the two CAPON isoforms in the proliferation of glioma cells in this study. Materials and Methods: Lentivirus-mediated stable cell lines with CAPON-L or CAPON-S overexpression were established in U87 and U251 glioma cells. Cell counting kit-8 and colony formation assays were used to evaluate cell proliferation. Western blot analysis of cell cycle-related proteins and flow cytometry were performed to analyze cell cycle progression. Some important molecules of the AKT/mTOR pathway and P53 were also measured by Western blot analysis. Results: Overexpression of CAPON-L showed a significantly inhibitory role in U251 cells, while it exhibited a promoting role in U87 cells. Consistently, overexpressing CAPON-L impeded the cell cycle progression and down-regulated the expression levels of Cyclin D1, CDK4 and CDK6 in U251 cells, whereas it up-regulated the CDK6 level in U87 cells. The overexpression of CAPON-L significantly decreased the phosphorylation and/or total levels of AKT, mTOR and S6 in U251 cells, while it did not affect these signaling molecules in U87 cells, except for a significant increase in the phosphorylation of AKT at Thr-308 site. Transfecting constitutively active AKT (myr-AKT) partially reversed the decreased phosphorylation of AKT and S6 in the CAPON-L-overexpressing U251 cells. In addition, we found a significant decrease in the wild-type P53 level in the CAPON-L-overexpressing U87 cells. The overexpression of CAPON-S also inhibited cell proliferation, blocked cell cycle progression, and decreased the AKT/mTOR pathway activity in U251 cells. Conclusion: The effects of CAPON-L overexpression on glioma cell proliferation are dependent on the AKT/mTOR/P53 activity. The overexpression of CAPON inhibits U251 cell proliferation through the AKT/mTOR signaling pathway, while overexpressing CAPON-L promoted U87 cell proliferation, possibly through down-regulating the P53 level.
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DOI：
10.1186/s40463-017-0187-1
发表时间：
2017-02-22
期刊：
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale
影响因子：
--
作者：
Alzahrani F;Clattenburg L;Muruganandan S;Bullock M;MacIsaac K;Wigerius M;Williams BA;Graham ME;Rigby MH;Trites JR;Taylor SM;Sinal CJ;Fawcett JP;Hart RD
通讯作者：
Hart RD
影响因子：
3.3
作者：
Shen, Aiguo;Gao, Shangfeng;Cheng, Chun
通讯作者：
Cheng, Chun
RASD1 过表达抑制胶质瘤细胞迁移/侵袭并失活 AKT/mTOR 信号通路
影响因子：
4.6
作者：
Gao S;Jin L;Liu G;Wang P;Sun Z;Cao Y;Shi H;Liu X;Shi Q;Zhou X;Yu R
通讯作者：
Yu R
影响因子：
--
作者：
Yaodong Shen;Hai-yan Liu;S. Gu;Ziwei Wei;Hong Liu
通讯作者：
Yaodong Shen;Hai-yan Liu;S. Gu;Ziwei Wei;Hong Liu
影响因子：
30.8
作者：
Arking, Dan E.;Pfeufer, Arne;Chakravarti, Aravinda
通讯作者：
Chakravarti, Aravinda