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siPRDX2-elevated DNM3 inhibits the proliferation and metastasis of colon cancer cells via AKT signaling pathway

Authors Ma Y, Guan L, Han Y, Zhou Y, Li X, Liu Y, Zhang X, Zhang W, Li X, Wang S, Lu W

Received 7 November 2018

Accepted for publication 9 May 2019

Published 28 June 2019 Volume 2019:11 Pages 5799—5811

DOI https://doi.org/10.2147/CMAR.S193805

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Professor Nakshatri


Yini Ma,1,2 Liying Guan,1 Yanxin Han,1 Yi Zhou,1 Xiaoming Li,1 Yumei Liu,1 Xiujuan Zhang,1 Weiying Zhang,1 Xiaohong Li,1 Shuhua Wang,1 Weidong Lu1

1Health Management Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, People’s Republic of China; 2Department of Nephrology, The Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan 250031, People’s Republic of China

Purpose: We have previously reported that PRDX2 plays an oncogenic role in colon cancer. In this study, the mRNA expression profile of PRDX2 in HCT116 cells was investigated. Furthermore, we selected Dynamin 3 (DNM3), which is up-regulated by siPRDX2, to investigate its expression pattern and functions in colon cancer.
Patients and methods: PRDX2 siRNA was transfected into HCT116 cells and the mRNA profile was tested by RNA-Sequencing. The expression of interest proteins was determined by Western blot. DNM3 expression in colon cancer tissues and para-carcinoma tissues was evaluated by Western blot and immunohistochemistry assays. Full-length cDNA of DNM3 was cloned into pcDNA3.1 and introduced into HCT116 and HT29 cells. Cell proliferation was tested by CCK-8 and colony formation assays. Cell invasion and migration were tested by transwell assays. Gelatin zymography was utilized for detection of MMP9 activity. Cell apoptosis was investigated with Annexin V/PI staining and flow cytometry and visualized with Hoechst/PI staining assay. All statistical analysis was performed with SPSS 17.0 software.
Results: PRDX2 knockdown led to 210 up-regulated genes and 16 down-regulated genes in HCT116 cells. We also found that DNM3 expression was up-regulated following PRDX2 silencing in HCT116 and HT29 cells. In colon cancer patients, DNM3 was down-regulated and showed a significant association with pathologic grading. DNM3 overexpression inhibited cell proliferation and induced apoptosis in HCT116 and HT29 cells. Cell migration and invasion were also down-regulated in DNM3 overexpressing colon cancer cells, which might be due to the inhibition of MMP9 proteolytic activities. After thorough investigation of the potential mechanism involved, we hypothesized that DNM3 overexpression induced activation of the mitochondrial apoptosis pathway and inhibition of the AKT pathway.
Conclusion: These data suggest that DNM3 is down-regulated in colon cancer, serving as a tumor suppressor. Our study provides new sights into the prognostic value and therapeutic application of DNM3 in colon cancer.

Keywords: mRNA expression profile, proliferation, invasion; migration, apoptosis, AKT

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