Cancer Medicine (Jun 2023)

Knockdown of kinesin family member 4A inhibits cell proliferation, migration, and invasion while promoting apoptosis of urothelial bladder carcinoma cells

  • Chen Zhang,
  • Maoyu Wang,
  • Yidie Ying,
  • Fang Meng,
  • Hongliang Gao,
  • Shuxiong Zeng,
  • Yasheng Zhu,
  • Anwei Liu,
  • Zhensheng Zhang,
  • Chuanliang Xu

DOI
https://doi.org/10.1002/cam4.5932
Journal volume & issue
Vol. 12, no. 11
pp. 12581 – 12592

Abstract

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Abstract Background 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. Methods 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. Results 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. Conclusions 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.

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