Cancer Management and Research (Apr 2019)

CDKN3 promotes tumor progression and confers cisplatin resistance via RAD51 in esophageal cancer

  • Wang J,
  • Che W,
  • Wang W,
  • Su G,
  • Zhen T,
  • Jiang Z

Journal volume & issue
Vol. Volume 11
pp. 3253 – 3264

Abstract

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Jiansong Wang,1 Wencheng Che,2 Weimin Wang,1 Gongzhang Su,3 Tianchang Zhen,3 Zhongmin Jiang31Graduate Department, Weifang Medical University, Weifang, Shandong 261031, People’s Republic of China; 2Department of Thoracic Surgery, Zibo Central Hospital, Zibo, Shandong 255022, People’s Republic of China; 3Department of Thoracic Surgery, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, People’s Republic of ChinaPurpose: Esophageal cancer (ESCA) progression and chemoresistance are critical factors that impact the survival of patients with esophageal cancer. Cyclin dependent kinase inhibitor 3 (CDKN3) is an important regulator of the cell cycle that has received little attention, therefore the purpose of this study was to investigate CDKN3 involvement in ESCA.Methods: We first explored the public database in addition to our cohort to evaluate the expression of CDKN3 in ESCA patients. We performed bioinformative analysis on specific processes regulated by CDKN3, then we investigated the role of CDKN3 in ESCA progression and chemoresistance in vitro and in vivo. Finally, we sought to elucidate the mechanism of CDKN3 regulation of chemoresistance in ESCA.Results: We discovered that CDKN3 was highly expressed in ESCA and serves as an independent prognostic factor of this disease. Bioinformatic analysis showed CDKN3 involvement in DNA replication, the cell cycle G2/M phase transition, DNA damage repair (DDR) signaling pathways, et al Functional experiments in vitro and in vivo demonstrated that CDKN3 promoted ESCA progression and enhanced cisplatin resistance. Furthermore, CDKN3 inhibition resulted in reduced expression of RAD51, which plays a pivotal role in DDR. Overexpression of RAD51 reversed cisplatin-induced DNA damage and chemosensitivity in CDKN3 inhibited ESCA cell lines.Conclusion: The present research indicated that CDKN3 promoted ESCA progression and enhanced cisplatin resistance via RAD51, thereby influencing overall patient survival.Keywords: esophageal cancer, chemoresistance, CDKN3, RAD51, DNA damage repair  

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