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Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance

In the human genome, miR‐451a, miR‐144‐5p (passenger strand), and miR‐144‐3p (guide strand) reside in clustered microRNA (miRNA) sequences located within the 17q11.2 region. Low expression of these miRNAs is significantly associated with poor prognosis of patients with renal cell carcinoma (RCC) (mi...

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Autores principales: Yamada, Yasutaka, Arai, Takayuki, Kojima, Satoko, Sugawara, Sho, Kato, Mayuko, Okato, Atsushi, Yamazaki, Kazuto, Naya, Yukio, Ichikawa, Tomohiko, Seki, Naohiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125479/
https://www.ncbi.nlm.nih.gov/pubmed/29968393
http://dx.doi.org/10.1111/cas.13722
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author Yamada, Yasutaka
Arai, Takayuki
Kojima, Satoko
Sugawara, Sho
Kato, Mayuko
Okato, Atsushi
Yamazaki, Kazuto
Naya, Yukio
Ichikawa, Tomohiko
Seki, Naohiko
author_facet Yamada, Yasutaka
Arai, Takayuki
Kojima, Satoko
Sugawara, Sho
Kato, Mayuko
Okato, Atsushi
Yamazaki, Kazuto
Naya, Yukio
Ichikawa, Tomohiko
Seki, Naohiko
author_sort Yamada, Yasutaka
collection PubMed
description In the human genome, miR‐451a, miR‐144‐5p (passenger strand), and miR‐144‐3p (guide strand) reside in clustered microRNA (miRNA) sequences located within the 17q11.2 region. Low expression of these miRNAs is significantly associated with poor prognosis of patients with renal cell carcinoma (RCC) (miR‐451a: P = .00305; miR‐144‐5p: P = .00128; miR‐144‐3p: P = 9.45 × 10(−5)). We previously reported that miR‐451a acted as an antitumor miRNA in RCC cells. Involvement of the passenger strand of the miR‐144 duplex in the pathogenesis of RCC is not well understood. Functional assays showed that miR‐144‐5p and miR‐144‐3p significantly reduced cancer cell migration and invasive abilities, suggesting these miRNAs acted as antitumor miRNAs in RCC cells. Analyses of miR‐144‐5p targets identified a total of 65 putative oncogenic targets in RCC cells. Among them, high expression levels of 9 genes (FAM64A, F2,TRIP13,ANKRD36,CENPF,NCAPG,CLEC2D,SDC3, and SEMA4B) were significantly associated with poor prognosis (P < .001). Among these targets, expression of SDC3 was directly controlled by miR‐144‐5p, and its expression enhanced cancer cell aggressiveness. We identified genes downstream by SDC3 regulation. Data showed that expression of 10 of the downstream genes (IL18RAP,SDC3,SH2D1A,GZMH,KIF21B,TMC8,GAB3,HLA‐DPB2,PLEK, and C1QB) significantly predicted poor prognosis of the patients (P = .0064). These data indicated that the antitumor miR‐144‐5p/oncogenic SDC3 axis was deeply involved in RCC pathogenesis. Clustered miRNAs (miR‐451a, miR‐144‐5p, and miR‐144‐3p) acted as antitumor miRNAs, and their targets were intimately involved in RCC pathogenesis.
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spelling pubmed-61254792018-09-10 Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance Yamada, Yasutaka Arai, Takayuki Kojima, Satoko Sugawara, Sho Kato, Mayuko Okato, Atsushi Yamazaki, Kazuto Naya, Yukio Ichikawa, Tomohiko Seki, Naohiko Cancer Sci Original Articles In the human genome, miR‐451a, miR‐144‐5p (passenger strand), and miR‐144‐3p (guide strand) reside in clustered microRNA (miRNA) sequences located within the 17q11.2 region. Low expression of these miRNAs is significantly associated with poor prognosis of patients with renal cell carcinoma (RCC) (miR‐451a: P = .00305; miR‐144‐5p: P = .00128; miR‐144‐3p: P = 9.45 × 10(−5)). We previously reported that miR‐451a acted as an antitumor miRNA in RCC cells. Involvement of the passenger strand of the miR‐144 duplex in the pathogenesis of RCC is not well understood. Functional assays showed that miR‐144‐5p and miR‐144‐3p significantly reduced cancer cell migration and invasive abilities, suggesting these miRNAs acted as antitumor miRNAs in RCC cells. Analyses of miR‐144‐5p targets identified a total of 65 putative oncogenic targets in RCC cells. Among them, high expression levels of 9 genes (FAM64A, F2,TRIP13,ANKRD36,CENPF,NCAPG,CLEC2D,SDC3, and SEMA4B) were significantly associated with poor prognosis (P < .001). Among these targets, expression of SDC3 was directly controlled by miR‐144‐5p, and its expression enhanced cancer cell aggressiveness. We identified genes downstream by SDC3 regulation. Data showed that expression of 10 of the downstream genes (IL18RAP,SDC3,SH2D1A,GZMH,KIF21B,TMC8,GAB3,HLA‐DPB2,PLEK, and C1QB) significantly predicted poor prognosis of the patients (P = .0064). These data indicated that the antitumor miR‐144‐5p/oncogenic SDC3 axis was deeply involved in RCC pathogenesis. Clustered miRNAs (miR‐451a, miR‐144‐5p, and miR‐144‐3p) acted as antitumor miRNAs, and their targets were intimately involved in RCC pathogenesis. John Wiley and Sons Inc. 2018-07-28 2018-09 /pmc/articles/PMC6125479/ /pubmed/29968393 http://dx.doi.org/10.1111/cas.13722 Text en © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Yamada, Yasutaka
Arai, Takayuki
Kojima, Satoko
Sugawara, Sho
Kato, Mayuko
Okato, Atsushi
Yamazaki, Kazuto
Naya, Yukio
Ichikawa, Tomohiko
Seki, Naohiko
Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance
title Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance
title_full Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance
title_fullStr Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance
title_full_unstemmed Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance
title_short Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance
title_sort regulation of antitumor mir‐144‐5p targets oncogenes: direct regulation of syndecan‐3 and its clinical significance
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125479/
https://www.ncbi.nlm.nih.gov/pubmed/29968393
http://dx.doi.org/10.1111/cas.13722
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