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

  • Lin Jing
  • Meng-En Zhai
  • Jian Cui
  • Xin-Yu Fan
  • Yuan-Yuan Cheng
  • Jian-Li JiangEmail author
  • Zhi-Nan ChenEmail author


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.


Cisplatin resistance CNOT3 Lung cancer Apoptosis RIPK3 



This work was supported by the National Basic Research Program of China (Grant No. 2015CB553701), and the National Science and Technology Major Project (Grant No. 2017ZX10203205-004-002).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

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Supplementary material 1 (DOCX 16 kb)
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Supplementary material 2 (TIFF 235 kb)
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Supplementary material 3 (TIFF 336 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • 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
    • 1
    • 2
    Email author
  • Zhi-Nan Chen
    • 1
    • 2
    Email author
  1. 1.National Translational Science Center for Molecular MedicineXi’anChina
  2. 2.Department of Cell Biology, School of Basic MedicineThe Fourth Military Medical UniversityXi’anChina
  3. 3.Department of Cardiovascular SurgeryXijing Hospital, The Fourth Military Medical UniversityXi’anChina

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