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padi3 induces cell cycle arrest via the Sirt2/AKT/p21 pathway and acts as a tumor suppressor gene in colon cancer

Cancer Biology & Medicine 2019年第4期16卷 729-742页

作者： Xiaotian Chang Zhengbin Chai Jiaorui Zou Hongxing Wang Yao Wang Yabing Zheng Hui Wu Chunyan Liu Medical Research Center The First Affiliated Hospital of Shandong First Medical UniversityJinan 250014 Medical Research Center of the Hospital Affiliated to Qingdao University Qingdao 266000China Department of Laboratory Medicine Jinan Infectious Disease HospitalShandong UniversityJinan 250021China

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 ***,the role of padi3 in colon cancer is *** this study,we investigated the function and molecular mechanism of padi3 in colon cancer ***:Western blot and real-time PCR were used to detect the expression levels of several ***-8,flow cytometry(FCM)and colony formation assays were used to examine cell proliferation,the cell cycle and colony formation *** 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 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)***3-expressing HCT116 cells had a lower tumor formation rate and produced smaller tumors than control ***3 significantly decreased Sirtuin2(Sirt2)and Snail expression and AKT phosphorylation and increased p21 expression,and Sirt2 overexpression partly reversed the effects induced by padi3 *** showed that padi3 is mainly localized in the *** mutation experiments showed that the C-domain is the key domain involved in the antitumor activity of ***: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.

关键词： padi3 Sirt2 colon cancer cell cycle C-domain

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