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TRIM32 overexpression improves chemoresistance through regulation of mitochondrial function in non-small-cell lung cancers

Authors Du Y, Zhang W, Du B, Zang S, Wang X, Mao X, Hu Z

Received 8 June 2018

Accepted for publication 21 August 2018

Published 5 November 2018 Volume 2018:11 Pages 7841—7852

DOI https://doi.org/10.2147/OTT.S176689

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Carlos E Vigil


Yaming Du,1,* Wei Zhang,1,* Binghui Du,1 Sheng Zang,1 Xinpeng Wang,1 Xin Mao,1 Zhansheng Hu2

1Department of Vascular Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China; 2Department of Intensive Care Unit, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China

*These authors contributed equally to this work

Background: TRIM32 is overexpressed in several human cancers. However, its expression pattern, biological characteristics and mechanisms in human non-small cell lung cancer (NSCLC) have not been reported.
Methods: We examined TRIM32 protein in 115 cases of NSCLC specimens. TRIM32 plasmid transfection and siRNA knockdown was carried out in NSCLC cell lines. AnnexinV/PI and JC-1 staining were performed to examine the change of apoptosis and mitochondrial membrane potential. Western blot was used to detect change of downstream proteins.
Results: We found that TRIM32 protein was upregulated in 69 cases and positively correlated with advanced TNM stage. TRIM32 overexpression also correlated with poor survival of NSCLC patients. Biological assays demonstrated that TRIM32 overexpression promoted while it depletion inhibited cell growth, colony formation and invasion. In addition, TRIM32 maintained NSCLC cell viability and reduced apoptosis when treated with cisplatin. JC-1 and CellRox staining demonstrated that TRIM32 could maintain mitochondrial membrane potential and reduce Reactive Oxygen Species (ROS) production after cisplatin treatment. Western blot analysis showed that TRIM32 overexpression downregulated caspase 3 cleavage and cytochrome c release. TRIM32 also positively regulated Bcl-2 protein expression and NF-κB signaling. Inhibition of NF-κB abolished the effects of TRIM32 on Bcl-2.
Conclusion: Taken together, our results indicated that TRIM32 is overexpressed in NSCLC and regulates cisplatin resistance, possibly through NF-κB and Bcl-2.

Keywords: NSCLC, TRIM32, NF-κB, apoptosis

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