Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.

<h4>Background</h4>Oral leukoplakia (OLK) is a potentially malignant disorder of the oral cavity. However, the underlying mechanism of OLK is still unclear. In this study, we explore possible miRNAs involved in OLK.<h4>Methodology/principal findings</h4>Using miRNA microarray...

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Autores principales:	Wen Xiao, Zhe-Xuan Bao, Chen-Yang Zhang, Xiao-Yun Zhang, Lin-Jun Shi, Zeng-Tong Zhou, Wei-Wen Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cfd873fb21c14d91812984c41da63dc3
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spelling	oai:doaj.org-article:cfd873fb21c14d91812984c41da63dc32021-11-18T07:15:18ZUpregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.1932-620310.1371/journal.pone.0038648https://doaj.org/article/cfd873fb21c14d91812984c41da63dc32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22719913/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Oral leukoplakia (OLK) is a potentially malignant disorder of the oral cavity. However, the underlying mechanism of OLK is still unclear. In this study, we explore possible miRNAs involved in OLK.<h4>Methodology/principal findings</h4>Using miRNA microarrays, we profiled miRNA expression in OLK and malignantly transformed OLK (mtOLK) tissue samples. The upregulation of miR-31, miR-142-5p, miR-33a, miR-1259, miR-146b-5p, miR-886-3p, miR-886-5p, miR-519d, and miR-301a along with the downregulation of miR-572, miR-611, miR-602, miR-675, miR-585, miR-623, miR-637, and miR-1184 in mtOLK were new observations. Fluorescence in situ hybridization (FISH) analyses confirmed that miR-31 is highly expressed in mtOLK. There was a significant difference between the FISH score (p<0.05) in patients with or without recurrent/newly formed OLK. Functional analyses demonstrated that a miR-31* inhibitor decreased apoptosis in the Leuk-1, which is an immortalized oral epithelial cell line spontaneously derived from an oral leukoplakia lesion. miR-31* regulated apoptosis, cell proliferation, migration, and invasion in the HOIEC, which is a HPV E6/E7-immortalized oral epithelial cell line. Furthermore, miR-31* modulated the biological functions of apoptosis, cell proliferation, cell cycle, migration, and invasion in the oral squamous cell carcinoma cell line, Cal-27. Using bioinformatic analyses and dual luciferase reporter assays, we determined that the 3' untranslated region of fibroblast growth factor 3 (FGF3) is the target of miR-31. Expression of FGF3 was downregulated or upregulated in the presence of a miR-31 mimic or inhibitor, respectively.<h4>Conclusions/significance</h4>Upregulation of miR-31* is negatively associated with recurrent/newly formed OLK. MiR-31* may exert similar but distinguishable effects on biological function in oral cells with different malignant potential. FGF3 is the target of miR-31. miR-31 may play an important role during OLK progression through regulating FGF3. MiRNA* strands may also have prominent roles in oral carcinogenesis.Wen XiaoZhe-Xuan BaoChen-Yang ZhangXiao-Yun ZhangLin-Jun ShiZeng-Tong ZhouWei-Wen JiangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e38648 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wen Xiao Zhe-Xuan Bao Chen-Yang Zhang Xiao-Yun Zhang Lin-Jun Shi Zeng-Tong Zhou Wei-Wen Jiang Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.
description	<h4>Background</h4>Oral leukoplakia (OLK) is a potentially malignant disorder of the oral cavity. However, the underlying mechanism of OLK is still unclear. In this study, we explore possible miRNAs involved in OLK.<h4>Methodology/principal findings</h4>Using miRNA microarrays, we profiled miRNA expression in OLK and malignantly transformed OLK (mtOLK) tissue samples. The upregulation of miR-31, miR-142-5p, miR-33a, miR-1259, miR-146b-5p, miR-886-3p, miR-886-5p, miR-519d, and miR-301a along with the downregulation of miR-572, miR-611, miR-602, miR-675, miR-585, miR-623, miR-637, and miR-1184 in mtOLK were new observations. Fluorescence in situ hybridization (FISH) analyses confirmed that miR-31 is highly expressed in mtOLK. There was a significant difference between the FISH score (p<0.05) in patients with or without recurrent/newly formed OLK. Functional analyses demonstrated that a miR-31* inhibitor decreased apoptosis in the Leuk-1, which is an immortalized oral epithelial cell line spontaneously derived from an oral leukoplakia lesion. miR-31* regulated apoptosis, cell proliferation, migration, and invasion in the HOIEC, which is a HPV E6/E7-immortalized oral epithelial cell line. Furthermore, miR-31* modulated the biological functions of apoptosis, cell proliferation, cell cycle, migration, and invasion in the oral squamous cell carcinoma cell line, Cal-27. Using bioinformatic analyses and dual luciferase reporter assays, we determined that the 3' untranslated region of fibroblast growth factor 3 (FGF3) is the target of miR-31. Expression of FGF3 was downregulated or upregulated in the presence of a miR-31 mimic or inhibitor, respectively.<h4>Conclusions/significance</h4>Upregulation of miR-31* is negatively associated with recurrent/newly formed OLK. MiR-31* may exert similar but distinguishable effects on biological function in oral cells with different malignant potential. FGF3 is the target of miR-31. miR-31 may play an important role during OLK progression through regulating FGF3. MiRNA* strands may also have prominent roles in oral carcinogenesis.
format	article
author	Wen Xiao Zhe-Xuan Bao Chen-Yang Zhang Xiao-Yun Zhang Lin-Jun Shi Zeng-Tong Zhou Wei-Wen Jiang
author_facet	Wen Xiao Zhe-Xuan Bao Chen-Yang Zhang Xiao-Yun Zhang Lin-Jun Shi Zeng-Tong Zhou Wei-Wen Jiang
author_sort	Wen Xiao
title	Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.
title_short	Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.
title_full	Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.
title_fullStr	Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.
title_full_unstemmed	Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.
title_sort	upregulation of mir-31* is negatively associated with recurrent/newly formed oral leukoplakia.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/cfd873fb21c14d91812984c41da63dc3
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Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.

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