Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients

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...

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Autores principales:	Eijiro Ueta, Koichiro Tsutsumi, Hironari Kato, Hiroshi Matsushita, Hidenori Shiraha, Masakuni Fujii, Kazuyuki Matsumoto, Shigeru Horiguchi, Hiroyuki Okada
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b91437c12a44036ae1637545c836f21
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spelling	oai:doaj.org-article:9b91437c12a44036ae1637545c836f212021-12-02T17:47:23ZExtracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients10.1038/s41598-021-91804-02045-2322https://doaj.org/article/9b91437c12a44036ae1637545c836f212021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91804-0https://doaj.org/toc/2045-2322Abstract 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.Eijiro UetaKoichiro TsutsumiHironari KatoHiroshi MatsushitaHidenori ShirahaMasakuni FujiiKazuyuki MatsumotoShigeru HoriguchiHiroyuki OkadaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eijiro Ueta Koichiro Tsutsumi Hironari Kato Hiroshi Matsushita Hidenori Shiraha Masakuni Fujii Kazuyuki Matsumoto Shigeru Horiguchi Hiroyuki Okada Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients
description	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.
format	article
author	Eijiro Ueta Koichiro Tsutsumi Hironari Kato Hiroshi Matsushita Hidenori Shiraha Masakuni Fujii Kazuyuki Matsumoto Shigeru Horiguchi Hiroyuki Okada
author_facet	Eijiro Ueta Koichiro Tsutsumi Hironari Kato Hiroshi Matsushita Hidenori Shiraha Masakuni Fujii Kazuyuki Matsumoto Shigeru Horiguchi Hiroyuki Okada
author_sort	Eijiro Ueta
title	Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients
title_short	Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients
title_full	Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients
title_fullStr	Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients
title_full_unstemmed	Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients
title_sort	extracellular vesicle-shuttled mirnas as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9b91437c12a44036ae1637545c836f21
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Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients

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