VPS53 Suppresses Malignant Properties in Colorectal Cancer by Inducing the Autophagy Signaling Pathway

Hong Peng; Jie Zheng; Qiang Su; Xueya Feng; Mingsha Peng; Lei Gong; Hong Wu; Xue Pan

doi:10.2147/OTT.S254823

VPS53 Suppresses Malignant Properties in Colorectal Cancer by Inducing the Autophagy Signaling Pathway

Onco Targets Ther. 2020 Oct 21:13:10667-10675. doi: 10.2147/OTT.S254823. eCollection 2020.

Authors

Hong Peng¹, Jie Zheng², Qiang Su³, Xueya Feng¹, Mingsha Peng¹, Lei Gong⁴, Hong Wu¹, Xue Pan⁵

Affiliations

¹ Department of Anorectal Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China.
² Department of Anesthesiology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China.
³ Department of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong Key Laboratory of Individualized Drug Therapy, Nanchong, Sichuan, 637000, People's Republic of China.
⁴ Department of Gastrointestinal Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China.
⁵ Scientific Research Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Abstract

Background: Many studies found that VPS53, one of the subunits of the golgi-associated retrograde protein (GARP) complexes, was aberrantly expressed in human diseases.

Aim: This study investigated the functions and molecular mechanisms of VPS53 in colorectal cancer (CRC).

Methods: Expression and correlation of Beclin 1 and VPS53 were analyzed by RT-qPCR and Pearson's correlation in CRC tissues, and VPS53 expression was also determined in CRC cells. The changes of proliferation, migration, invasion, apoptosis, and autophagy of CRC cells were examined by a succession of functional experiments including CCK-8, flow cytometry, transwell assay, and electron microscopy. The levels of autophagy related proteins were evaluated by Western blotting analysis.

Results: RT-qPCR results found that VPS53 was downregulated in CRC tissues and cells, and Beclin 1 expression was also decreased in CRC tissues. There was a positive correlation between VPS53 and Beclin 1. Functional results showed that overexpression of VPS53 could suppress proliferation, migration, and invasion, and accelerate apoptosis and autophagy of CRC cells. Also, VPS53 could upregulate Beclin 1 and LC3BII, suggesting the inductive effect of VPS53 on CRC cell autophagy. Furthermore, it was found that the autophagy inhibitor (Inhb) could attenuate the inhibition of VPS53 on CRC progression.

Conclusion: VPS53 repressed CRC progression by regulating the autophagy signaling pathway, suggesting that VPS53 might be a promising therapeutic target for CRC.

Keywords: VPS53; autophagy; cell invasion; cell migration; colorectal cancer.

Grants and funding

This work was supported by North Sichuan Medical College City school cooperation program (18SXHZ0364, 18SXHZ0408, 19SXHZ0297); Science and Technology Research Project of Sichuan Province (2017JY0116); School Grade Research Key Project of North Sichuan Medical College (CBY18-A-ZD13), and Basic Scientific and Technological Strategic Cooperation of Nanchong Municipal Schools (NSMC20170311).