Cargando…

TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility

Distant metastasis leads oral cancer patients into a poor survival rate and a high recurrence stage. During tumor progression, dysregulated microRNAs (miRNAs) have been reported to involve tumor initiation and modulate oral cancer malignancy. MiR-450a was significantly upregulated in oral squamous c...

Descripción completa

Detalles Bibliográficos
Autores principales: Hsing, En-Wei, Shiah, Shine-Gwo, Peng, Hsuan-Yu, Chen, Ya-Wen, Chuu, Chih-Pin, Hsiao, Jenn-Ren, Lyu, Ping-Chiang, Chang, Jang-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426234/
https://www.ncbi.nlm.nih.gov/pubmed/30893332
http://dx.doi.org/10.1371/journal.pone.0213463
_version_ 1783404975123070976
author Hsing, En-Wei
Shiah, Shine-Gwo
Peng, Hsuan-Yu
Chen, Ya-Wen
Chuu, Chih-Pin
Hsiao, Jenn-Ren
Lyu, Ping-Chiang
Chang, Jang-Yang
author_facet Hsing, En-Wei
Shiah, Shine-Gwo
Peng, Hsuan-Yu
Chen, Ya-Wen
Chuu, Chih-Pin
Hsiao, Jenn-Ren
Lyu, Ping-Chiang
Chang, Jang-Yang
author_sort Hsing, En-Wei
collection PubMed
description Distant metastasis leads oral cancer patients into a poor survival rate and a high recurrence stage. During tumor progression, dysregulated microRNAs (miRNAs) have been reported to involve tumor initiation and modulate oral cancer malignancy. MiR-450a was significantly upregulated in oral squamous cell carcinoma (OSCC) patients without functional reports. This study was attempted to uncover the molecular mechanism of novel miR-450a in OSCC. Mir-450a expression was examined by quantitative RT-PCR, both in OSCC cell lines and patients. Specific target of miR-450a was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-450a and TMEM182 were accessed by adhesion and transwell invasion analyses. Determination of the expression and cellular localization of TMEM182 was examined by RT-PCR and by immunofluorescence staining. The signaling pathways involved in regulation of miR-450a were investigated using the kinase inhibitors. Overexpression of miR-450a in OSCC cells impaired cell adhesion ability and induced invasiveness, which demonstrated the functional role of miR-450a as an onco-miRNA. Interestingly, tumor necrosis factor alpha (TNF-α)-mediated expression of TMEM182 was regulated by miR-450a induction. MiR-450a-reduced cellular adhesion was abolished by TMEM182 restoration. Furthermore, the oncogenic activity of TNF-α/miR-450a/TMEM182 axis was primarily through activating extracellular signal–regulated kinase 1/2 (ERK1/2) signaling pathway. ERK1/2 inhibitor prevented the TNF-α-induced miR-450a expression and enhanced adhesion ability. Our data suggested that TNF-α-induced ERK1/2-dependent miR-450a against TMEM182 expression exerted a great influence on increasing OSCC motility. Overall, our results provide novel molecular insights into how TNF-α contributes to oral carcinogenesis through miR-450a that targets TMEM182.
format Online
Article
Text
id pubmed-6426234
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-64262342019-04-02 TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility Hsing, En-Wei Shiah, Shine-Gwo Peng, Hsuan-Yu Chen, Ya-Wen Chuu, Chih-Pin Hsiao, Jenn-Ren Lyu, Ping-Chiang Chang, Jang-Yang PLoS One Research Article Distant metastasis leads oral cancer patients into a poor survival rate and a high recurrence stage. During tumor progression, dysregulated microRNAs (miRNAs) have been reported to involve tumor initiation and modulate oral cancer malignancy. MiR-450a was significantly upregulated in oral squamous cell carcinoma (OSCC) patients without functional reports. This study was attempted to uncover the molecular mechanism of novel miR-450a in OSCC. Mir-450a expression was examined by quantitative RT-PCR, both in OSCC cell lines and patients. Specific target of miR-450a was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-450a and TMEM182 were accessed by adhesion and transwell invasion analyses. Determination of the expression and cellular localization of TMEM182 was examined by RT-PCR and by immunofluorescence staining. The signaling pathways involved in regulation of miR-450a were investigated using the kinase inhibitors. Overexpression of miR-450a in OSCC cells impaired cell adhesion ability and induced invasiveness, which demonstrated the functional role of miR-450a as an onco-miRNA. Interestingly, tumor necrosis factor alpha (TNF-α)-mediated expression of TMEM182 was regulated by miR-450a induction. MiR-450a-reduced cellular adhesion was abolished by TMEM182 restoration. Furthermore, the oncogenic activity of TNF-α/miR-450a/TMEM182 axis was primarily through activating extracellular signal–regulated kinase 1/2 (ERK1/2) signaling pathway. ERK1/2 inhibitor prevented the TNF-α-induced miR-450a expression and enhanced adhesion ability. Our data suggested that TNF-α-induced ERK1/2-dependent miR-450a against TMEM182 expression exerted a great influence on increasing OSCC motility. Overall, our results provide novel molecular insights into how TNF-α contributes to oral carcinogenesis through miR-450a that targets TMEM182. Public Library of Science 2019-03-20 /pmc/articles/PMC6426234/ /pubmed/30893332 http://dx.doi.org/10.1371/journal.pone.0213463 Text en © 2019 Hsing et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hsing, En-Wei
Shiah, Shine-Gwo
Peng, Hsuan-Yu
Chen, Ya-Wen
Chuu, Chih-Pin
Hsiao, Jenn-Ren
Lyu, Ping-Chiang
Chang, Jang-Yang
TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility
title TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility
title_full TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility
title_fullStr TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility
title_full_unstemmed TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility
title_short TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility
title_sort tnf-α-induced mir-450a mediates tmem182 expression to promote oral squamous cell carcinoma motility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426234/
https://www.ncbi.nlm.nih.gov/pubmed/30893332
http://dx.doi.org/10.1371/journal.pone.0213463
work_keys_str_mv AT hsingenwei tnfainducedmir450amediatestmem182expressiontopromoteoralsquamouscellcarcinomamotility
AT shiahshinegwo tnfainducedmir450amediatestmem182expressiontopromoteoralsquamouscellcarcinomamotility
AT penghsuanyu tnfainducedmir450amediatestmem182expressiontopromoteoralsquamouscellcarcinomamotility
AT chenyawen tnfainducedmir450amediatestmem182expressiontopromoteoralsquamouscellcarcinomamotility
AT chuuchihpin tnfainducedmir450amediatestmem182expressiontopromoteoralsquamouscellcarcinomamotility
AT hsiaojennren tnfainducedmir450amediatestmem182expressiontopromoteoralsquamouscellcarcinomamotility
AT lyupingchiang tnfainducedmir450amediatestmem182expressiontopromoteoralsquamouscellcarcinomamotility
AT changjangyang tnfainducedmir450amediatestmem182expressiontopromoteoralsquamouscellcarcinomamotility