title: Profiling of downregulated blood-circulating miR-150-5p as a novel tumor marker for cholangiocarcinoma.
abstract: Altered microRNA (miRNA) expression plays a role in cholangiocarcinoma (CCA) development; thus, detection of blood-circulating miRNAs could be useful as CCA markers. This study profiled serum miRNA levels in patients with primary sclerosing cholangitis (PSC) and CCA and then assessed the role of miR-150-5p in CCA progression in vitro. Three samples were randomly selected from each of 50 sera of healthy controls, 30 PSC sera, and 28 CCA sera with matched bile samples for miRNA microarray profiling. The dysregulated miRNAs were confirmed using qRT-PCR, and miR-150-5p was selected for further in vitro and ex vivo studies. The miRNA microarray identified three dysregulated miRNAs in both CCA and PSC samples, while miR-150-5p level was consistently lower in CCA sera, bile, and tissues than in normal control and PSC sera (P < 0.05). Furthermore, levels of miR-150-5p were associated with serum carbohydrate antigen 19-9 (CA19-9) levels and CCA pathological grade. Bioinformatic Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses showed that miR-150-5p could regulate hand-full gene pathways, including cancer pathway (P < 0.01). However, overexpression of miR-150-5p inhibited proliferation, migration, and invasion capability of CCA cells (P < 0.05). Luciferase reporter assay showed that miR-150-5p bound to an oncogene Ets including gene-1 (ELK1), and Western blot data confirmed that miR-150-5p suppressed ELK1 expression in CCA cell lines. These results suggest that reduced miR-150-5p expression could contribute to CCA development and progression due to uncontrolled ELK1 expression. Thus, further study could evaluate miR-150-5p as a novel target and predictor for CCA prevention and treatment.
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, China.
authors.forename: Xiongbo
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, China.
authors.forename: Dayang
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, China.
authors.forename: Zhifa
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Medical School of Soochow University, Suzhou, 215123, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Medical School of Soochow University, Suzhou, 215123, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Xuzhou NO.1 People's Hospital, Xuzhou, Jiangsu, 221002, China. gx_chen2010@163.com.
authors.forename: Guangxia
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, China. wdf8025@163.com.
authors.forename: Fangmei
authors.initials: F
authors.lastname: An
mesh_terms: D017209:Apoptosis; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D015536:Down-Regulation; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; C533097:MIR150, human
keywords: Cholangiocarcinoma; Tumor invasion; miR-150-5p; miRNA profiling