PMID- 34018826 OWN - NLM STAT- MEDLINE DCOM- 20210525 LR - 20220531 IS - 1473-2300 (Electronic) IS - 0300-0605 (Print) IS - 0300-0605 (Linking) VI - 49 IP - 5 DP - 2021 May TI - Agrin expression is correlated with tumor development and poor prognosis in cholangiocarcinoma. PG - 3000605211009722 LID - 10.1177/03000605211009722 [doi] LID - 03000605211009722 AB - OBJECTIVE: This study examined the role of agrin in the development of cholangiocarcinoma (CCA). METHODS: Western blotting was performed to detect the expression of target genes. The correlation between agrin expression and prognosis was analyzed using the Kaplan-Meier method. Proliferation, migration, invasion, and tumorigenesis were examined in CCA cells and tissues using the Cell Counting Kit-8 assay, cell cycle analysis, transwell migration assay, and nude mouse tumorigenicity assay in vivo, respectively. RESULTS: Agrin expression was significantly upregulated in CCA tissues compared with that in adjacent non-tumor tissues, and agrin expression was correlated with poorer tumor characteristics such as portal vein tumor thrombus, intrahepatic metastasis, and worse survival. Forced agrin expression in CCA cells apparently promoted proliferation, colony formation, migration, invasion, and cell cycle progression, but agrin depletion had the opposite effects. Furthermore, agrin-depleted CCA cells developed fewer and smaller tumors than control cells in vivo. Mechanistic analyses indicated that agrin activated the Hippo signaling pathway and induced the translocation of YAP to the nucleus. CONCLUSIONS: Agrin promoted CCA progression by activating the Hippo signaling pathway, suggesting its promise as a target for CCA therapy. FAU - He, Meimei AU - He M AD - Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou University, Wenzhou, 325000, Zhejiang Province, China. FAU - Cheng, Chen AU - Cheng C AD - Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou University, Wenzhou, 325000, Zhejiang Province, China. FAU - Tu, Junxue AU - Tu J AD - Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou University, Wenzhou, 325000, Zhejiang Province, China. FAU - Ji, Sha-Sha AU - Ji SS AD - Department of Pharmacy, Shaoxing Traditional Chinese Medicine Hospital, Shaoxing, Zhejiang Province, China. FAU - Lou, Dan AU - Lou D AUID- ORCID: 0000-0002-9269-4737 AD - Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou University, Wenzhou, 325000, Zhejiang Province, China. FAU - Bai, Binglong AU - Bai B AD - Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou University, Wenzhou, 325000, Zhejiang Province, China. LA - eng PT - Journal Article PL - England TA - J Int Med Res JT - The Journal of international medical research JID - 0346411 RN - 0 (Agrin) SB - IM MH - Agrin MH - Animals MH - *Bile Duct Neoplasms/genetics MH - Bile Ducts, Intrahepatic MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - *Cholangiocarcinoma/genetics MH - Gene Expression Regulation, Neoplastic MH - Mice MH - Prognosis PMC - PMC8150497 OTO - NOTNLM OT - Cholangiocarcinoma OT - Hippo pathway OT - YAP OT - agrin OT - invasion OT - metastasis OT - proliferation OT - tumorigenesis COIS- Declaration of conflicting interest: The authors declare that there is no conflict of interest. EDAT- 2021/05/22 06:00 MHDA- 2021/05/26 06:00 PMCR- 2021/05/21 CRDT- 2021/05/21 12:12 PHST- 2021/05/21 12:12 [entrez] PHST- 2021/05/22 06:00 [pubmed] PHST- 2021/05/26 06:00 [medline] PHST- 2021/05/21 00:00 [pmc-release] AID - 10.1177_03000605211009722 [pii] AID - 10.1177/03000605211009722 [doi] PST - ppublish SO - J Int Med Res. 2021 May;49(5):3000605211009722. doi: 10.1177/03000605211009722.