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Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma

Our recent studies of microRNA (miRNA) expression signatures indicated that microRNA-29a (miR-29a) was significantly downregulated in several types of human cancers, suggesting that miR-29a may be a putative tumor-suppressive miRNA in human cancers. The aim of this study was to investigate the funct...

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Autores principales: YAMAMOTO, NORIKO, KINOSHITA, TAKASHI, NOHATA, NIJIRO, YOSHINO, HIROFUMI, ITESAKO, TOSHIHIKO, FUJIMURA, LISA, MITSUHASHI, AKIRA, USUI, HIROKAZU, ENOKIDA, HIDEKI, NAKAGAWA, MASAYUKI, SHOZU, MAKIO, SEKI, NAOHIKO
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834344/
https://www.ncbi.nlm.nih.gov/pubmed/24141696
http://dx.doi.org/10.3892/ijo.2013.2145
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author YAMAMOTO, NORIKO
KINOSHITA, TAKASHI
NOHATA, NIJIRO
YOSHINO, HIROFUMI
ITESAKO, TOSHIHIKO
FUJIMURA, LISA
MITSUHASHI, AKIRA
USUI, HIROKAZU
ENOKIDA, HIDEKI
NAKAGAWA, MASAYUKI
SHOZU, MAKIO
SEKI, NAOHIKO
author_facet YAMAMOTO, NORIKO
KINOSHITA, TAKASHI
NOHATA, NIJIRO
YOSHINO, HIROFUMI
ITESAKO, TOSHIHIKO
FUJIMURA, LISA
MITSUHASHI, AKIRA
USUI, HIROKAZU
ENOKIDA, HIDEKI
NAKAGAWA, MASAYUKI
SHOZU, MAKIO
SEKI, NAOHIKO
author_sort YAMAMOTO, NORIKO
collection PubMed
description Our recent studies of microRNA (miRNA) expression signatures indicated that microRNA-29a (miR-29a) was significantly downregulated in several types of human cancers, suggesting that miR-29a may be a putative tumor-suppressive miRNA in human cancers. The aim of this study was to investigate the functional significance of miR-29a in cervical squamous cell carcinoma (SCC) and to identify novel miR-29a-regulated cancer pathways and target genes involved in cervical SCC oncogenesis and metastasis. Restoration of miR-29a in cervical cancer cell lines (CaSKi, HeLa, ME180 and Yumoto) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that heat-shock protein 47 (HSP47), a member of the serpin superfamily of serine proteinase inhibitors and a molecular chaperone involved in the maturation of collagen molecules, was a potential target of miR-29a regulation. Luciferase reporter assays showed that miR-29a directly regulated HSP47. Moreover, silencing of the HSP47 gene significantly inhibited cell migration and invasion in cancer cells and the expression of HSP47 was upregulated in cancer tissues and cervical intraepithelial neoplasia (CIN), as demonstrated by immunostaining. Downregulation of miR-29a was a frequent event in cervical SCC and miR-29a acted as a tumor suppressor by directly targeting HSP47. Recognition of tumor-suppressive miRNA-regulated molecular targets provides new insights into the potential mechanisms of cervical SCC oncogenesis and metastasis and suggests novel therapeutic strategies for treatment of this disease.
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spelling pubmed-38343442013-11-20 Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma YAMAMOTO, NORIKO KINOSHITA, TAKASHI NOHATA, NIJIRO YOSHINO, HIROFUMI ITESAKO, TOSHIHIKO FUJIMURA, LISA MITSUHASHI, AKIRA USUI, HIROKAZU ENOKIDA, HIDEKI NAKAGAWA, MASAYUKI SHOZU, MAKIO SEKI, NAOHIKO Int J Oncol Articles Our recent studies of microRNA (miRNA) expression signatures indicated that microRNA-29a (miR-29a) was significantly downregulated in several types of human cancers, suggesting that miR-29a may be a putative tumor-suppressive miRNA in human cancers. The aim of this study was to investigate the functional significance of miR-29a in cervical squamous cell carcinoma (SCC) and to identify novel miR-29a-regulated cancer pathways and target genes involved in cervical SCC oncogenesis and metastasis. Restoration of miR-29a in cervical cancer cell lines (CaSKi, HeLa, ME180 and Yumoto) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that heat-shock protein 47 (HSP47), a member of the serpin superfamily of serine proteinase inhibitors and a molecular chaperone involved in the maturation of collagen molecules, was a potential target of miR-29a regulation. Luciferase reporter assays showed that miR-29a directly regulated HSP47. Moreover, silencing of the HSP47 gene significantly inhibited cell migration and invasion in cancer cells and the expression of HSP47 was upregulated in cancer tissues and cervical intraepithelial neoplasia (CIN), as demonstrated by immunostaining. Downregulation of miR-29a was a frequent event in cervical SCC and miR-29a acted as a tumor suppressor by directly targeting HSP47. Recognition of tumor-suppressive miRNA-regulated molecular targets provides new insights into the potential mechanisms of cervical SCC oncogenesis and metastasis and suggests novel therapeutic strategies for treatment of this disease. D.A. Spandidos 2013-10-18 /pmc/articles/PMC3834344/ /pubmed/24141696 http://dx.doi.org/10.3892/ijo.2013.2145 Text en Copyright © 2013, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
YAMAMOTO, NORIKO
KINOSHITA, TAKASHI
NOHATA, NIJIRO
YOSHINO, HIROFUMI
ITESAKO, TOSHIHIKO
FUJIMURA, LISA
MITSUHASHI, AKIRA
USUI, HIROKAZU
ENOKIDA, HIDEKI
NAKAGAWA, MASAYUKI
SHOZU, MAKIO
SEKI, NAOHIKO
Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma
title Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma
title_full Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma
title_fullStr Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma
title_full_unstemmed Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma
title_short Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma
title_sort tumor-suppressive microrna-29a inhibits cancer cell migration and invasion via targeting hsp47 in cervical squamous cell carcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834344/
https://www.ncbi.nlm.nih.gov/pubmed/24141696
http://dx.doi.org/10.3892/ijo.2013.2145
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