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Authors Wang J, Che W, Wang W, Su G, Zhen T, Jiang Z
Received 7 November 2018
Accepted for publication 5 March 2019
Published 15 April 2019 Volume 2019:11 Pages 3253—3264
DOI https://doi.org/10.2147/CMAR.S193793
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Dr Kenan Onel
Purpose: 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