PMID- 31284679 OWN - NLM STAT- MEDLINE DCOM- 20200430 LR - 20200430 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 9 IP - 7 DP - 2019 Jul 7 TI - Roles of Zinc Finger Protein 423 in Proliferation and Invasion of Cholangiocarcinoma through Oxidative Stress. LID - 10.3390/biom9070263 [doi] LID - 263 AB - Zinc finger protein 423 (ZNF423) is a transcriptional factor involved in the development and progression of cancers but has not yet been examined in cholangiocarcinoma (CCA), an oxidative stress-driven cancer of biliary epithelium. In this study, we hypothesized that oxidative stress mediated ZNF423 expression regulates its downstream genes resulting in CCA genesis. ZNF423 protein expression patterns and 8-oxodG (an oxidative stress marker) formation in CCA tissues were investigated using immunohistochemical analysis. The results showed that ZNF423 was overexpressed in CCA cells compared to normal bile duct cells adjacent of the tumor. Notably, ZNF423 expression was positively correlated with 8-oxodG formation. Moreover, ZNF423 expression in an immortalized cholangiocyte cell line (MMNK1) was increased by hydrogen peroxide-treatment, suggesting that oxidative stress induces ZNF423 expression. To investigate the roles of ZNF423 in CCA progression, ZNF423 mRNA was silenced using specific siRNA in CCA cell lines, KKU-100 and KKU-213. Silencing of ZNF423 significantly inhibits cell proliferation and invasion of both CCA cell lines. Taking all these results together, the present study denoted that ZNF423 is an oxidative stress-responsive gene with an oncogenic property contributing to the regulation of CCA genesis. FAU - Chaiprasert, Timpika AU - Chaiprasert T AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Armartmuntree, Napat AU - Armartmuntree N AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Techasen, Anchalee AU - Techasen A AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand. AD - Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Sakonsinsiri, Chadamas AU - Sakonsinsiri C AUID- ORCID: 0000-0003-0145-8753 AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Pinlaor, Somchai AU - Pinlaor S AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand. AD - Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Ungarreevittaya, Piti AU - Ungarreevittaya P AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand. AD - Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Khuntikeo, Narong AU - Khuntikeo N AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand. AD - Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Namwat, Nisana AU - Namwat N AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Thanan, Raynoo AU - Thanan R AUID- ORCID: 0000-0002-9001-1197 AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. raynoo@kku.ac.th. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand. raynoo@kku.ac.th. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190707 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (Proteins) RN - 0 (ornithine decarboxylase antizyme) SB - IM MH - Bile Duct Neoplasms/genetics/*metabolism/pathology MH - Cell Line, Tumor MH - Cell Proliferation MH - Cholangiocarcinoma/genetics/*metabolism/pathology MH - Humans MH - *Oxidative Stress MH - Proteins/genetics/*metabolism PMC - PMC6681239 OTO - NOTNLM OT - cancer progression OT - cholangiocarcinoma OT - oxidative stress OT - zinc finger protein 423 (ZNF423) COIS- The authors declare no conflict of interest. EDAT- 2019/07/10 06:00 MHDA- 2020/05/01 06:00 PMCR- 2019/07/01 CRDT- 2019/07/10 06:00 PHST- 2019/05/16 00:00 [received] PHST- 2019/06/26 00:00 [revised] PHST- 2019/07/03 00:00 [accepted] PHST- 2019/07/10 06:00 [entrez] PHST- 2019/07/10 06:00 [pubmed] PHST- 2020/05/01 06:00 [medline] PHST- 2019/07/01 00:00 [pmc-release] AID - biom9070263 [pii] AID - biomolecules-09-00263 [pii] AID - 10.3390/biom9070263 [doi] PST - epublish SO - Biomolecules. 2019 Jul 7;9(7):263. doi: 10.3390/biom9070263.