PMID- 34494080 OWN - NLM STAT- MEDLINE DCOM- 20220128 LR - 20220128 IS - 1347-6947 (Electronic) IS - 0916-8451 (Linking) VI - 85 IP - 11 DP - 2021 Oct 21 TI - Overexpression of AGR2vH, an oncogenic AGR2 spliced transcript, potentiates tumorigenicity and proteomic alterations in cholangiocarcinoma cell. PG - 2263-2273 LID - 10.1093/bbb/zbab156 [doi] AB - The upregulation of anterior gradient 2 (AGR2) has been observed in cholangiocarcinoma (CCA) cells, nras-mutant zebrafish, and specimens derived from CCA patients. Our previous study reported AGR2 splicing into AGR2vH to facilitate CCA cell aggressiveness, while this work aims to investigate the molecular mechanisms underlying AGR2vH. First, AGR2vH upregulation was demonstrated in CCA tissues derived from patients. For in vitro studies, established AGR2vH-overexpressing KKU-213A cells were found to exhibit increased proliferation and clonogenicity. In vivo tumorigenicity assessed in a mouse model represented higher tumorigenic potential in AGR2vH-overexpressing cell xenograft mice. Next, LC-MS/MS was analyzed, indicating that AGR2vH may be associated with CCA cell proliferation via Wnt/beta-catenin signaling pathway activation, which was verified by beta-catenin expression and nuclear translocation. The current results provide evidence that AGR2vH upregulation promotes tumorigenicity in CCA cells linked with an alteration of CCA cell proteome. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry. FAU - Yosudjai, Juthamas AU - Yosudjai J AD - Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand. FAU - Inpad, Chaturong AU - Inpad C AD - Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand. FAU - Pothipan, Phattarin AU - Pothipan P AD - Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand. FAU - Saisomboon, Saowaluk AU - Saisomboon S AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Surangkul, Damrasamon AU - Surangkul D AD - Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand. FAU - Phimsen, Suchada AU - Phimsen S AD - Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand. FAU - Hongsrichan, Nuttanan AU - Hongsrichan N AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Wongkham, Sopit AU - Wongkham S AUID- ORCID: 0000-0001-9578-3041 AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Jirawatnotai, Siwanon AU - Jirawatnotai S AD - Siriraj Center of Research for Excellence for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. FAU - Roytrakul, Sittiruk AU - Roytrakul S AD - National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand. FAU - Kaewkong, Worasak AU - Kaewkong W AUID- ORCID: 0000-0002-7130-5827 AD - Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. LA - eng GR - Naresuan University/ GR - Thailand Research Fund/ GR - TRF-MRG6080014/Office of the Higher Education Commission/ GR - National Research Council of Thailand/ GR - NRCT5-RSA63011-04/NRCT-Research Career Development/ PT - Journal Article PL - England TA - Biosci Biotechnol Biochem JT - Bioscience, biotechnology, and biochemistry JID - 9205717 SB - IM MH - *Proteomics OTO - NOTNLM OT - AGR2 OT - alternative splicing OT - cholangiocarcinoma OT - proteomics OT - tumorigenesis EDAT- 2021/09/09 06:00 MHDA- 2022/01/29 06:00 CRDT- 2021/09/08 06:55 PHST- 2021/07/08 00:00 [received] PHST- 2021/09/02 00:00 [accepted] PHST- 2021/09/09 06:00 [pubmed] PHST- 2022/01/29 06:00 [medline] PHST- 2021/09/08 06:55 [entrez] AID - 6366227 [pii] AID - 10.1093/bbb/zbab156 [doi] PST - ppublish SO - Biosci Biotechnol Biochem. 2021 Oct 21;85(11):2263-2273. doi: 10.1093/bbb/zbab156.