ATG3, a Target of miR-431-5p, Promotes Proliferation and Invasion of Colon Cancer via Promoting Autophagy

Wei Huang; Chong Zeng; Shanbiao Hu; Lei Wang; Jie Liu

doi:10.2147/CMAR.S226828

ATG3, a Target of miR-431-5p, Promotes Proliferation and Invasion of Colon Cancer via Promoting Autophagy

Cancer Manag Res. 2019 Dec 9:11:10275-10285. doi: 10.2147/CMAR.S226828. eCollection 2019.

Authors

Wei Huang^{1

2}, Chong Zeng³, Shanbiao Hu⁴, Lei Wang⁵, Jie Liu¹

Affiliations

¹ Department of Pathology, Changsha Central Hospital, Changsha, Hunan, People's Republic of China.
² Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
³ Department of Respiratory and Neurology, Hunan Rongjun Hospital, Changsha, Hunan, People's Republic of China.
⁴ Department of Urological Organ Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
⁵ Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, People's Republic of China.

Abstract

Background: Studies have indicated that ATG3 could mediate the effects of other tumor-related regulators in carcinogenesis. However, the expression, role, and mechanism of ATG3 itself in cancers are rarely revealed. Thus, we explored the expression, function, and mechanism of ATG3 in colon cancer.

Materials and methods: The expression of ATG3 was detected in colon cancer tissues and cell lines, as well as in adjacent tumor tissues and normal colon epithelial cells. The effects of ATG3 alteration on proliferation and invasion were further analyzed. The expression and role of miR-431-5p, a potential negative regulator of ATG3, were also studied. Eventually, the role of autophagy in ATG3 related effects in colon cancer was checked.

Results: ATG3 is upregulated in colon cancer tissues and cells demonstrated by qPCR and IHC. ATG3 knockdown significantly suppressed proliferation and invasion of colon cancer cells indicated by plate clone formation and Transwell invasion assays. The expression of miR-431-5p is downregulated and negatively correlates with ATG3 in colon cancer. Furthermore, luciferase report system, plate clone formation and Transwell invasion assays demonstrated that miR-431-5p could prohibit cell proliferation and invasion via directly targeting ATG3 in colon cancer. Eventually, Western blot, plate clone formation and Transwell invasion assays proved that autophagy block could antagonize the promotive functions of ATG3 on proliferation and invasion in cancer suggesting autophagy activation accounts for the promotive role of ATG3 on proliferation and invasion in colon cancer.

Conclusion: Collectively, ATG3 upregulation, caused by downregulated miR-435-5p, promotes proliferation and invasion via an autophagy-dependent manner in colon cancer suggesting that miR-431-5p/ATG3/autophagy may be a potential therapeutic target in colon cancer.

Keywords: ATG3; autophagy; colon cancer; invasion; miR-431-5p; proliferation.