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Kinesin 12 (KIF15) contributes to the development and tumorigenicity of prostate cancer
Biochemical and Biophysical Research Communications ( IF 3.1 ) Pub Date : 2021-08-28 , DOI: 10.1016/j.bbrc.2021.08.072
Zeeshan Qureshi 1 , Mashaal Ahmad 2 , Wan-Xi Yang 1 , Fu-Qing Tan 3
Affiliation  

In Asia, prostate cancer is becoming a growing concern, impacting both socially and economically, compared with what is seen in western countries. Hence, it is essential to know the mechanisms associated with the development and tumorigenesis of PCa for primary diagnosis, risk management, and development of therapy strategies against PCa. Kinesin family member 15 (KIF15), a kinesin family member, is a plus-end-directed kinesin that functions to form bipolar spindles. There is emerging evidence indicating that KIF15 plays a significant role in several malignancies, such as pancreatic cancer, hepatocellular carcinoma, lung adenocarcinoma, and breast cancer. Still, the function of KIF15 remains unclear in prostate cancer. Here, we study the functional importance of KIF15 in the tumorigenesis of PCa. The bioinformatic analysis from PCa patients revealed high KIF15 expression compared to normal prostate tissues. High expression hinting at a possible functional role of KIF15 in regulating cell proliferation of PCa, which was demonstrated by both in vitro and in vivo assays. Downregulation of KIF15 silenced the expression of CDK2, p-RB, and Cyclin D1 and likewise blocked the cells at the G1 stage of the cell cycle. In addition, KIF15 downregulation inhibited MEK-ERK signaling by significantly silencing p-ERK and p-MEK levels. In conclusion, this study confirmed the functional significance of KIF15 in the growth and development of prostate cancer and could be a novel therapeutic target for the treatment of PCa.



中文翻译:

驱动蛋白 12 (KIF15) 有助于前列腺癌的发展和致瘤性

在亚洲,与西方国家相比,前列腺癌正日益受到关注,对社会和经济都产生影响。因此,了解与 PCa 发生和肿瘤发生相关的机制对于 PCa 的初步诊断、风险管理和治疗策略的开发至关重要。驱动蛋白家族成员 15 (KIF15) 是驱动蛋白家族成员,是一种加末端导向的驱动蛋白,其功能是形成双极纺锤体。有新的证据表明 KIF15 在多种恶性肿瘤中发挥重要作用,例如胰腺癌、肝细胞癌、肺腺癌和乳腺癌。尽管如此,KIF15 在前列腺癌中的功能仍不清楚。在这里,我们研究了 KIF15 在 PCa 肿瘤发生中的功能重要性。来自 PCa 患者的生物信息学分析显示,与正常前列腺组织相比,KIF15 表达较高。高表达暗示 KIF15 在调节 PCa 细胞增殖中可能具有功能作用,这由两者都证明体外体内试验。KIF15 的下调使 CDK2、p-RB 和细胞周期蛋白 D1 的表达沉默,同样在细胞周期的 G1 阶段阻断细胞。此外,KIF15 下调通过显着沉默 p-ERK 和 p-MEK 水平来抑制 MEK-ERK 信号传导。总之,本研究证实了 KIF15 在前列腺癌的生长和发展中的功能意义,可能成为治疗 PCa 的新治疗靶点。

更新日期:2021-08-31
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