PT - JOURNAL ARTICLE AU - Chang, Xiaotian AU - Chai, Zhengbin AU - Zou, Jiaorui AU - Wang, Hongxing AU - Wang, Yao AU - Zheng, Yabing AU - Wu, Hui AU - Liu, Chunyan TI - PADI3 induces cell cycle arrest <em>via</em> the Sirt2/AKT/p21 pathway and acts as a tumor suppressor gene in colon cancer AID - 10.20892/j.issn.2095-3941.2019.0065 DP - 2019 Nov 01 TA - Cancer Biology and Medicine PG - 729--742 VI - 16 IP - 4 4099 - http://www.cancerbiomed.org/content/16/4/729.short 4100 - http://www.cancerbiomed.org/content/16/4/729.full SO - Cancer Biol Med2019 Nov 01; 16 AB - Objective As a member of the peptidyl arginine deiminase (PAD) family, PADI3 is weakly expressed in colon cancer tissues and highly expressed in adjacent colon cancer tissues. However, the role of PADI3 in colon cancer is unclear. In this study, we investigated the function and molecular mechanism of PADI3 in colon cancer tumorigenesis.Methods Western blot and real-time PCR were used to detect the expression levels of several genes. CCK-8, flow cytometry (FCM) and colony formation assays were used to examine cell proliferation, the cell cycle and colony formation ability. RNA-sequencing analysis was used to study the molecular mechanism of PADI3 in tumorigenesis. A truncation mutation experiment was performed to determine the key functional domain of PADI3.Results PADI3 overexpression inhibited cell proliferation and colony formation and led to G1 phase arrest in both HCT116 (originating from primary colon cancer) and LoVo (originating from metastatic tumor nodules of colon cancer) cells. PADI3-expressing HCT116 cells had a lower tumor formation rate and produced smaller tumors than control cells. PADI3 significantly decreased Sirtuin2 (Sirt2) and Snail expression and AKT phosphorylation and increased p21 expression, and Sirt2 overexpression partly reversed the effects induced by PADI3 overexpression. Immunocytochemistry showed that PADI3 is mainly localized in the cytoplasm. Truncation mutation experiments showed that the C-domain is the key domain involved in the antitumor activity of PADI3.Conclusions PADI3 suppresses Snail expression and AKT phosphorylation and promotes p21 expression by downregulating Sirt2 expression in the cytoplasm, and the C-domain is the key domain for its antitumor activity.