Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility

<i>Background:</i> Knowledge on the role of miR changes in tumor stroma for cancer progression is limited. This study aimed to investigate the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC). <i>Methodology:</i> CAF and...

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Autores principales:	Saroj Rajthala, Anjie Min, Himalaya Parajuli, Kala Chand Debnath, Borghild Ljøkjel, Kristin Marie Hoven, Arild Kvalheim, Stein Lybak, Evelyn Neppelberg, Olav Karsten Vintermyr, Anne Christine Johannessen, Dipak Sapkota, Daniela Elena Costea
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	oral squamous cell carcinoma miR-204 fibroblasts tumor stroma ITGA11 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/effe369824c044b091b058fc650fb079
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spelling	oai:doaj.org-article:effe369824c044b091b058fc650fb0792021-11-11T17:22:47ZProfiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility10.3390/ijms2221119601422-00671661-6596https://doaj.org/article/effe369824c044b091b058fc650fb0792021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11960https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067<i>Background:</i> Knowledge on the role of miR changes in tumor stroma for cancer progression is limited. This study aimed to investigate the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC). <i>Methodology:</i> CAF and normal oral fibroblasts (NOFs) were isolated from biopsies of OSCC patients and healthy individuals after informed consent and grown in 3D collagen gels. Total RNA was extracted. Global miR expression was profiled using Illumina version 2 panels. The functional impact of altered miR-204 expression in fibroblasts on their phenotype and molecular profile was investigated using mimics and inhibitors of miR-204. Further, the impact of miR-204 expression in fibroblasts on invasion of adjacent OSCC cells was assessed in 3D-organotypic co-cultures. <i>Results:</i> Unsupervised hierarchical clustering for global miR expression resulted in separate clusters for CAF and NOF. SAM analysis identified differential expression of twelve miRs between CAF and NOF. Modulation of miR-204 expression did not affect fibroblast cell proliferation, but resulted in changes in the motility phenotype, expression of various motility-related molecules, and invasion of the adjacent OSCC cells. 3′ UTR miR target reporter assay showed ITGA11 to be a direct target of miR-204. <i>Conclusions:</i> This study identifies differentially expressed miRs in stromal fibroblasts of OSCC lesions compared with normal oral mucosa and it reveals that one of the significantly downregulated miRs in CAF, miR-204, has a tumor-suppressive function through inhibition of fibroblast migration by modulating the expression of several different molecules in addition to directly targeting ITGA11.Saroj RajthalaAnjie MinHimalaya ParajuliKala Chand DebnathBorghild LjøkjelKristin Marie HovenArild KvalheimStein LybakEvelyn NeppelbergOlav Karsten VintermyrAnne Christine JohannessenDipak SapkotaDaniela Elena CosteaMDPI AGarticleoral squamous cell carcinomamiR-204fibroblaststumor stromaITGA11Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11960, p 11960 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oral squamous cell carcinoma miR-204 fibroblasts tumor stroma ITGA11 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	oral squamous cell carcinoma miR-204 fibroblasts tumor stroma ITGA11 Biology (General) QH301-705.5 Chemistry QD1-999 Saroj Rajthala Anjie Min Himalaya Parajuli Kala Chand Debnath Borghild Ljøkjel Kristin Marie Hoven Arild Kvalheim Stein Lybak Evelyn Neppelberg Olav Karsten Vintermyr Anne Christine Johannessen Dipak Sapkota Daniela Elena Costea Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility
description	<i>Background:</i> Knowledge on the role of miR changes in tumor stroma for cancer progression is limited. This study aimed to investigate the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC). <i>Methodology:</i> CAF and normal oral fibroblasts (NOFs) were isolated from biopsies of OSCC patients and healthy individuals after informed consent and grown in 3D collagen gels. Total RNA was extracted. Global miR expression was profiled using Illumina version 2 panels. The functional impact of altered miR-204 expression in fibroblasts on their phenotype and molecular profile was investigated using mimics and inhibitors of miR-204. Further, the impact of miR-204 expression in fibroblasts on invasion of adjacent OSCC cells was assessed in 3D-organotypic co-cultures. <i>Results:</i> Unsupervised hierarchical clustering for global miR expression resulted in separate clusters for CAF and NOF. SAM analysis identified differential expression of twelve miRs between CAF and NOF. Modulation of miR-204 expression did not affect fibroblast cell proliferation, but resulted in changes in the motility phenotype, expression of various motility-related molecules, and invasion of the adjacent OSCC cells. 3′ UTR miR target reporter assay showed ITGA11 to be a direct target of miR-204. <i>Conclusions:</i> This study identifies differentially expressed miRs in stromal fibroblasts of OSCC lesions compared with normal oral mucosa and it reveals that one of the significantly downregulated miRs in CAF, miR-204, has a tumor-suppressive function through inhibition of fibroblast migration by modulating the expression of several different molecules in addition to directly targeting ITGA11.
format	article
author	Saroj Rajthala Anjie Min Himalaya Parajuli Kala Chand Debnath Borghild Ljøkjel Kristin Marie Hoven Arild Kvalheim Stein Lybak Evelyn Neppelberg Olav Karsten Vintermyr Anne Christine Johannessen Dipak Sapkota Daniela Elena Costea
author_facet	Saroj Rajthala Anjie Min Himalaya Parajuli Kala Chand Debnath Borghild Ljøkjel Kristin Marie Hoven Arild Kvalheim Stein Lybak Evelyn Neppelberg Olav Karsten Vintermyr Anne Christine Johannessen Dipak Sapkota Daniela Elena Costea
author_sort	Saroj Rajthala
title	Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility
title_short	Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility
title_full	Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility
title_fullStr	Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility
title_full_unstemmed	Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility
title_sort	profiling and functional analysis of microrna deregulation in cancer-associated fibroblasts in oral squamous cell carcinoma depicts an anti-invasive role of microrna-204 via regulation of their motility
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/effe369824c044b091b058fc650fb079
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Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility

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