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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Main Authors: Liping Wang, Yunxin Chen, Yongyong Yan, Xueqi Guo, Ying Fang, Yucheng Su, Lijing Wang, Janak L. Pathak, Linhu Ge
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2020.585976/full
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author Liping Wang
Yunxin Chen
Yongyong Yan
Yongyong Yan
Xueqi Guo
Ying Fang
Yucheng Su
Lijing Wang
Lijing Wang
Janak L. Pathak
Janak L. Pathak
Linhu Ge
Linhu Ge
author_facet Liping Wang
Yunxin Chen
Yongyong Yan
Yongyong Yan
Xueqi Guo
Ying Fang
Yucheng Su
Lijing Wang
Lijing Wang
Janak L. Pathak
Janak L. Pathak
Linhu Ge
Linhu Ge
author_sort Liping Wang
collection DOAJ
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 doaj.art-6e2a1f4ba11d4d7cb20c626bf6b0c3e42022-12-21T20:14:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-11-011010.3389/fonc.2020.585976585976miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTTLiping Wang0Yunxin Chen1Yongyong Yan2Yongyong Yan3Xueqi Guo4Ying Fang5Yucheng Su6Lijing Wang7Lijing Wang8Janak L. Pathak9Janak L. Pathak10Linhu Ge11Linhu Ge12Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, ChinaInstitute of Oral Disease, Guangzhou Medical University, Guangzhou, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, ChinaChinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, ChinaSchool of Life Science and Biopharmaceutics, Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, ChinaInstitute of Oral Disease, Guangzhou Medical University, Guangzhou, ChinaAffiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, ChinaInstitute of Oral Disease, Guangzhou Medical University, Guangzhou, ChinaHuntingtin (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.https://www.frontiersin.org/articles/10.3389/fonc.2020.585976/fulloral squamous cell carcinomamir-146aHuntington genemigrationinvasionmetastasis
spellingShingle Liping Wang
Yunxin Chen
Yongyong Yan
Yongyong Yan
Xueqi Guo
Ying Fang
Yucheng Su
Lijing Wang
Lijing Wang
Janak L. Pathak
Janak L. Pathak
Linhu Ge
Linhu Ge
miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT
Frontiers in Oncology
oral squamous cell carcinoma
mir-146a
Huntington gene
migration
invasion
metastasis
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 oral squamous cell carcinoma
mir-146a
Huntington gene
migration
invasion
metastasis
url https://www.frontiersin.org/articles/10.3389/fonc.2020.585976/full
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