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Ueta, Eijiro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Tsutsumi, Koichiro Department of Gastroenterology, Okayama University Hospital ORCID Kaken ID researchmap
Kato, Hironari Department of Gastroenterology, Okayama University Hospital ORCID Kaken ID researchmap
Matsushita, Hiroshi Department of Gastroenterology, Okayama University Hospital
Shiraha, Hidenori Department of Gastroenterology, Okayama University Hospital Kaken ID publons researchmap
Fujii, Masakuni Department of Internal Medicine, Okayama Saiseikai General Hospital
Matsumoto, Kazuyuki Department of Gastroenterology, Okayama University Hospital ORCID Kaken ID publons
Horiguchi, Shigeru Department of Gastroenterology, Okayama University Hospital
Okada, Hiroyuki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kaken ID publons researchmap
Abstract
Circulating microRNAs (miRNAs) in serum extracellular vesicles (EVs) are a promising biomarker in cancer. We aimed to elucidate the serum EVs miRNA biomarkers to identify patients with gallbladder cancer (GBC) and to clarify their potential roles. One hundred nineteen serum EVs from GBC and non-GBC individuals were isolated by pure-EVs-yieldable size-exclusion chromatography, and then were analyzed using a comprehensive miRNAs array and RT-qPCR-based validation. The functional roles of the identified miRNAs were also investigated using GBC cell lines. Serum EVs miR-1246 and miR-451a were significantly upregulated and downregulated, respectively in GBC patients (P=0.005 and P=0.001), in line with their expression levels in cancer tissue according to an in silico analysis. The combination of CEA and CA19-9 with miR-1246 showed the highest diagnostic power (AUC, 0.816; Sensitivity, 72.0%; Specificity, 90.8%), and miR-1246 was an independent prognostic marker of GBC (Hazard ratio, 3.05; P=0.017) according to a Cox proportional hazards model. In vitro, miR-1246 promoted cell proliferation and invasion, while miR-451a inhibited cell proliferation and induced apoptosis with the targeting of MIF, PSMB8 and CDKN2D. Taken together, miR-1246 in serum EVs has potential application as a diagnostic and prognostic marker and miR-451a may be a novel therapeutic target in GBC.
Published Date
2021-06-10
Publication Title
Scientific Reports
Volume
volume11
Issue
issue1
Publisher
Nature Research
Start Page
12298
ISSN
2045-2322
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© The Author(s) 2021
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publisher
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1038/s41598-021-91804-0
License
http://creativecommons.org/licenses/by/4.0/
Funder Name
Japan Society for the Promotion of Science
助成番号
JP18H06223
JP19K08423