Knockdown of kinesin family member 4A inhibits cell proliferation, migration, and invasion while promoting apoptosis of urothelial bladder carcinoma cells.
Knockdown of kinesin family member 4A inhibits cell proliferation, migration, and invasion while promoting apoptosis of urothelial bladder carcinoma cells.
复制标题
DOI：
10.1002/cam4.5932
复制
发表时间：
2023-06
期刊：
影响因子：
4
通讯作者：
Xu, Chuanliang
中科院分区：
文献类型：
--
作者：
Zhang, Chen;Wang, Maoyu;Ying, Yidie;Meng, Fang;Gao, Hongliang;Zeng, Shuxiong;Zhu, Yasheng;Liu, Anwei;Zhang, Zhensheng;Xu, Chuanliang
关键词：
驱动蛋白家族成员4A（KIF 4A）在多种癌症中上调。然而，其在膀胱尿路上皮癌（UBC）中的表达和潜在的下游靶点仍不清楚。从GEPIA数据库下载KIF 4A在UBC和非癌组织中的表达数据。使用伤口愈合、transwell、集落形成、CCK-8和流式细胞术测定来检查T24和5637 UBC细胞的细胞增殖、迁移、侵袭和凋亡。使用qRT-PCR、蛋白质印迹分析和免疫组织化学分析KIF 4A和潜在下游基因。在UBC样本中，KIF 4A表达显著高于相应的非癌样本。KIF 4A高表达的UBC患者的癌症特异性生存期和总生存期较差。KIF 4A基因的敲低可显著抑制UBC细胞的增殖并促进其凋亡，同时伴有AKT的去磷酸化和促凋亡因子的蛋白水平升高。此外，KIF 4A的敲除减少了UBC细胞的迁移和侵袭，而KIF 4A的过表达则表现出相反的作用，并且沿着改变了上皮-间充质转化相关基因的蛋白水平。此外，在UBC细胞中，过表达YAP 1促进KIF 4A表达，而敲低YAP 1抑制KIF 4A表达。或者，KIF 4A敲低降低YAP 1核蛋白水平，而KIF 4A过表达抑制YAP 1磷酸化并促进YAP 1核转位。KIF 4A表达上调与UBC预后不良相关。KIF 4A的敲除抑制UBC细胞的增殖、迁移和侵袭，同时可能通过AKT的去磷酸化、EMT相关基因的改变以及与YAP 1的相互作用诱导细胞凋亡。
Kinesin family member 4A (KIF4A) is upregulated in a variety of cancers. However, its expression and potential downstream targets in urothelial bladder carcinoma (UBC) remain unclear. Expression data of KIF4A in UBC and noncancerous tissues were downloaded from the GEPIA database. Cell proliferation, migration, invasion, and apoptosis of T24 and 5637 UBC cells were examined using wound healing, transwell, colony formation, CCK‐8, and flow cytometry assays. KIF4A and potential downstream genes were analyzed using qRT‐PCR, western blot analysis, and immunohistochemistry. In UBC samples, KIF4A expression was significantly higher than in corresponding noncancerous samples. UBC patients with high KIF4A expression had poor cancer‐specific survival and overall survival. Knockdown of KIF4A significantly inhibited proliferation and promoted apoptosis of UBC cells, accompanied by dephosphorylation of AKT and increased the protein level of proapoptotic factors. Additionally, knockdown of KIF4A reduced migration and invasion of UBC cells whereas overexpression of KIF4A exhibited opposite effects, along with altered protein level in epithelial‐mesenchymal transition‐related genes. Furthermore, overexpression of YAP1 promoted KIF4A expression whereas knockdown of YAP1 suppressed KIF4A expression in UBC cells. Alternatively, KIF4A knockdown reduced YAP1 nuclear protein level whereas KIF4A overexpression suppressed YAP1 phosphorylation and facilitated YAP1 nuclear translocation. KIF4A upregulation correlates with poor prognosis of UBC. Knockdown of KIF4A inhibits proliferation, migration, and invasion of UBC cells while inducing apoptosis possibly through dephosphorylation of AKT, changes in EMT‐related genes, and interaction with YAP1.
登录
查看更多内容
河马效应子YAP促进了对RAF和MEK靶向的癌症疗法的耐药性。
影响因子：
30.8
作者：
Lin L;Sabnis AJ;Chan E;Olivas V;Cade L;Pazarentzos E;Asthana S;Neel D;Yan JJ;Lu X;Pham L;Wang MM;Karachaliou N;Cao MG;Manzano JL;Ramirez JL;Torres JM;Buttitta F;Rudin CM;Collisson EA;Algazi A;Robinson E;Osman I;Muñoz-Couselo E;Cortes J;Frederick DT;Cooper ZA;McMahon M;Marchetti A;Rosell R;Flaherty KT;Wargo JA;Bivona TG
通讯作者：
Bivona TG
靶向 KIF4A/AR 轴逆转去势抵抗性前列腺癌的内分泌治疗抵抗
影响因子：
11.5
作者：
Cao, Qi;Song, Zhengshuai;Zhang, Xiaoping
通讯作者：
Zhang, Xiaoping
影响因子：
6.4
作者：
Roseweir, A. K.;Kong, C. Y.;Roxburgh, C. S.
通讯作者：
Roxburgh, C. S.
影响因子：
5.4
作者：
Zheng, Pengyi;Wu, Kaijie;Han, Qingjiang
通讯作者：
Han, Qingjiang
影响因子：
9.2
作者：
Li Y;Sun C;Tan Y;Zhang H;Li Y;Zou H
通讯作者：
Zou H