PMID- 29212264 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 55 DP - 2017 Nov 7 TI - CR6-interacting factor 1 inhibits invasiveness by suppressing TGF-beta-mediated epithelial-mesenchymal transition in hepatocellular carcinoma. PG - 94759-94768 LID - 10.18632/oncotarget.21925 [doi] AB - CR6-interacting factor 1 (CRIF1) regulates cell cycle progression and the DNA damage response. Here, we show that CRIF1 expression is decreased in hepatocellular carcinoma (HCC) tissues and positively correlates with patients' survival. In vitro, down-regulation of CRIF1 promotes HCC cell proliferation and invasiveness, while over-expression has the opposite effect. in vivo, CRIF1 knockdown enhances growth of HCC xenografts. Analysis of mRNA microarrays showed that CRIF1 knockdown activates genes involved in TGF-beta RI/Smad2/3 signaling, leading to epithelial-mesenchymal transition (EMT) and increased matrix metalloproteinase-3 (MMP3) expression. However, cell invasion and EMT are abrogated in HCC cells treated with SB525334, a specific TGF-beta RI inhibitor, which indicates the inhibitory effect of CRIF1 on HCC tumor growth is mediated by TGF-beta signaling. These results demonstrate that CRIF1 benefits patient survival by inhibiting HCC cell invasiveness through suppression of TGF-beta-mediated EMT and MMP3 expression. This suggests CRIF1 may serve as a novel target for inhibiting HCC metastasis. FAU - Zhuang, Runzhou AU - Zhuang R AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Lu, Di AU - Lu D AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Zhuo, Jianyong AU - Zhuo J AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Zhang, Xuanyu AU - Zhang X AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Wang, Kun AU - Wang K AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Wei, Xuyong AU - Wei X AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Wei, Qiang AU - Wei Q AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Wang, Wei AU - Wang W AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Xie, Haiyang AU - Xie H AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Zhou, Lin AU - Zhou L AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Xu, Xiao AU - Xu X AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. FAU - Zheng, Shusen AU - Zheng S AD - Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. AD - Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. LA - eng PT - Journal Article DEP - 20171019 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 PMC - PMC5706910 OTO - NOTNLM OT - CR6-interacting factor 1 OT - EMT OT - TGF-beta OT - hepatocellular carcinoma COIS- CONFLICTS OF INTEREST No potential conflicts of interest were disclosed. EDAT- 2017/12/08 06:00 MHDA- 2017/12/08 06:01 PMCR- 2017/11/07 CRDT- 2017/12/08 06:00 PHST- 2017/05/13 00:00 [received] PHST- 2017/08/09 00:00 [accepted] PHST- 2017/12/08 06:00 [entrez] PHST- 2017/12/08 06:00 [pubmed] PHST- 2017/12/08 06:01 [medline] PHST- 2017/11/07 00:00 [pmc-release] AID - 21925 [pii] AID - 10.18632/oncotarget.21925 [doi] PST - epublish SO - Oncotarget. 2017 Oct 19;8(55):94759-94768. doi: 10.18632/oncotarget.21925. eCollection 2017 Nov 7.