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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2013
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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. |
format | Online Article Text |
id | pubmed-3834344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
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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