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miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT

Huntingtin (HTT) is one of the target genes of miR-146-a and regulates various cancer cell activities. This study aims to explore the miR-146a expression pattern in oral squamous cell carcinoma (OSCC) and its role and mechanism in OSCC progression and metastasis via targeting the HTT gene. OSCC tiss...

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Autores principales: Wang, Liping, Chen, Yunxin, Yan, Yongyong, Guo, Xueqi, Fang, Ying, Su, Yucheng, Wang, Lijing, Pathak, Janak L., Ge, Linhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691531/
https://www.ncbi.nlm.nih.gov/pubmed/33282738
http://dx.doi.org/10.3389/fonc.2020.585976
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author Wang, Liping
Chen, Yunxin
Yan, Yongyong
Guo, Xueqi
Fang, Ying
Su, Yucheng
Wang, Lijing
Pathak, Janak L.
Ge, Linhu
author_facet Wang, Liping
Chen, Yunxin
Yan, Yongyong
Guo, Xueqi
Fang, Ying
Su, Yucheng
Wang, Lijing
Pathak, Janak L.
Ge, Linhu
author_sort Wang, Liping
collection PubMed
description Huntingtin (HTT) is one of the target genes of miR-146-a and regulates various cancer cell activities. This study aims to explore the miR-146a expression pattern in oral squamous cell carcinoma (OSCC) and its role and mechanism in OSCC progression and metastasis via targeting the HTT gene. OSCC tissue and non-cancerous matched tissue (NCMT) were obtained from 14 patients. OSCC cell lines and normal HOK cells were used to analyze migration and invasion assay. OSCC-induced miR-146a knockout mice (B6.Cg-Mir146tm1.1Bal) model was developed. Transwell cell migration/invasion and scratch wound assays were used to investigate the OSCC cell migration and invasion in vitro. Kaplan-Meier survival analysis was used to investigate the association of HTT expression patterns in cancer tissue with patient survival percentage and duration. Pearson’s correlation analysis tested the association between miR-146a and HTT expression in OSCC tissues. miR-146a mimic and inhibitor transfection were performed to overexpress and knockdown the miR-146a in OSCC cells, respectively. miR-146a expression was highly upregulated in OSCC tissues and OSCC cell lines. Cancer cell migration/invasion was enhanced in miR-146a overexpressed cells and reduced in mi-R146a knockdowned cells. HTT expression was reduced in OSCC tissues and cell lines compared to NCMT and HOK cells, respectively. HTT expression was downregulated in miR-146a overexpressed OSCC cells and upregulated in miR-146a knockdowned OSCC cells. The expression pattern of miR-146a in OSCC cell lines and tissues was inversely correlated with HTT expression. Prediction of miRNA target analysis showed that HTT possesses the binding sites for miR-146a. HTT overexpression in OSCC tissues was associated with patients’ higher survival percentage and duration. HTT knockdown in OSCC cells enhanced miR-146a expression and cell migration/invasion. Inducing OSCC in miR-146a knockout mice increased the HTT expression in tongue tissue and alleviated the cancer aggressiveness and epithelial damage. Overexpressed miR-146a in OSCC targets the HTT gene and enhances cancer cell migration/invasion unraveling the possible role of HTT in miR146a-mediated OSCC cell migration and invasion.
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spelling pubmed-76915312020-12-04 miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT Wang, Liping Chen, Yunxin Yan, Yongyong Guo, Xueqi Fang, Ying Su, Yucheng Wang, Lijing Pathak, Janak L. Ge, Linhu Front Oncol Oncology Huntingtin (HTT) is one of the target genes of miR-146-a and regulates various cancer cell activities. This study aims to explore the miR-146a expression pattern in oral squamous cell carcinoma (OSCC) and its role and mechanism in OSCC progression and metastasis via targeting the HTT gene. OSCC tissue and non-cancerous matched tissue (NCMT) were obtained from 14 patients. OSCC cell lines and normal HOK cells were used to analyze migration and invasion assay. OSCC-induced miR-146a knockout mice (B6.Cg-Mir146tm1.1Bal) model was developed. Transwell cell migration/invasion and scratch wound assays were used to investigate the OSCC cell migration and invasion in vitro. Kaplan-Meier survival analysis was used to investigate the association of HTT expression patterns in cancer tissue with patient survival percentage and duration. Pearson’s correlation analysis tested the association between miR-146a and HTT expression in OSCC tissues. miR-146a mimic and inhibitor transfection were performed to overexpress and knockdown the miR-146a in OSCC cells, respectively. miR-146a expression was highly upregulated in OSCC tissues and OSCC cell lines. Cancer cell migration/invasion was enhanced in miR-146a overexpressed cells and reduced in mi-R146a knockdowned cells. HTT expression was reduced in OSCC tissues and cell lines compared to NCMT and HOK cells, respectively. HTT expression was downregulated in miR-146a overexpressed OSCC cells and upregulated in miR-146a knockdowned OSCC cells. The expression pattern of miR-146a in OSCC cell lines and tissues was inversely correlated with HTT expression. Prediction of miRNA target analysis showed that HTT possesses the binding sites for miR-146a. HTT overexpression in OSCC tissues was associated with patients’ higher survival percentage and duration. HTT knockdown in OSCC cells enhanced miR-146a expression and cell migration/invasion. Inducing OSCC in miR-146a knockout mice increased the HTT expression in tongue tissue and alleviated the cancer aggressiveness and epithelial damage. Overexpressed miR-146a in OSCC targets the HTT gene and enhances cancer cell migration/invasion unraveling the possible role of HTT in miR146a-mediated OSCC cell migration and invasion. Frontiers Media S.A. 2020-11-13 /pmc/articles/PMC7691531/ /pubmed/33282738 http://dx.doi.org/10.3389/fonc.2020.585976 Text en Copyright © 2020 Wang, Chen, Yan, Guo, Fang, Su, Wang, Pathak and Ge http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wang, Liping
Chen, Yunxin
Yan, Yongyong
Guo, Xueqi
Fang, Ying
Su, Yucheng
Wang, Lijing
Pathak, Janak L.
Ge, Linhu
miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT
title miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT
title_full miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT
title_fullStr miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT
title_full_unstemmed miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT
title_short miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT
title_sort mir-146a overexpression in oral squamous cell carcinoma potentiates cancer cell migration and invasion possibly via targeting htt
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691531/
https://www.ncbi.nlm.nih.gov/pubmed/33282738
http://dx.doi.org/10.3389/fonc.2020.585976
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