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

Hong Peng,1 Jie Zheng,2 Qiang Su,3 Xueya Feng,1 Mingsha Peng,1 Lei Gong,4 Hong Wu,1 Xue Pan5 1Department of Anorectal Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 2Department of Anesthesiology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 3Department 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; 4Department of Gastrointestinal Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 5Scientific Research Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Xue PanScientific Research Department, The First Affiliated Hospital of Chongqing Medical University, No. 1 of Youyi Road, Yuanjiagang, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86 13594002025Email panxue89012705@163.comBackground: 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: colorectal cancer, VPS53, autophagy, cell migration, cell invasion