2. Academic Validation
  3. CNOT3 contributes to cisplatin resistance in lung cancer through inhibiting RIPK3 expression

CNOT3 contributes to cisplatin resistance in lung cancer through inhibiting RIPK3 expression

  • Apoptosis. 2019 Aug;24(7-8):673-685. doi: 10.1007/s10495-019-01550-y.
Lin Jing 1 2,  Meng-En Zhai 3,  Jian Cui 1 2,  Xin-Yu Fan 1 2,  Yuan-Yuan Cheng 1 2,  Jian-Li Jiang 4 5,  Zhi-Nan Chen 6 7
Affiliations

Affiliations

  • 1 National Translational Science Center for Molecular Medicine, Xi'an, 710032, China.
  • 2 Department of Cell Biology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, 710032, China.
  • 3 Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
  • 4 National Translational Science Center for Molecular Medicine, Xi'an, 710032, China. jiangjl@fmmu.edu.cn.
  • 5 Department of Cell Biology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, 710032, China. jiangjl@fmmu.edu.cn.
  • 6 National Translational Science Center for Molecular Medicine, Xi'an, 710032, China. znchen@fmmu.edu.cn.
  • 7 Department of Cell Biology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, 710032, China. znchen@fmmu.edu.cn.
PMID: 31177396 DOI: 10.1007/s10495-019-01550-y
Abstract

Chemotherapeutic resistance always results in poor clinical outcomes of Cancer patients and its intricate mechanisms are large obstacles in overcoming drug resistance. CCR4-NOT transcription complex subunit 3 (CNOT3), a post-translational regulator, is suggested to be involved in Cancer development and progression. However, its role in chemotherapeutic resistance is not well understood. In this study, after screening the CNOT3 mRNA in a Cancer microarray database called Oncomine and examining the expression levels of CNOT3 mRNA in normal tissues and lung Cancer tissues, we found that CNOT3 was up-regulated in lung Cancer tissues. Besides, its high-expression was associated with poor prognosis of lung Cancer patients. We also found higher expression level of CNOT3 and lower expression level of receptor-interacting protein kinase 3 (RIPK3) in cisplatin-resistant A549 (A549/DDP) cells, and knocking down CNOT3 expression could sensitize A549/DDP cells to cisplatin-induced Apoptosis. We demonstrated that CNOT3 depletion up-regulated the expression level of RIPK3 and the enhanced Apoptosis was mediated by the elevated RIPK3 to further trigger Caspase 8 activation. Taken together, our results reveal a role of CNOT3 in cisplatin resistance of lung Cancer and provide a potential target for lung Cancer therapy.

Keywords

Apoptosis; CNOT3; Cisplatin resistance; Lung cancer; RIPK3.

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