%A Wang,Liping %A Chen,Yunxin %A Yan,Yongyong %A Guo,Xueqi %A Fang,Ying %A Su,Yucheng %A Wang,Lijing %A Pathak,Janak L. %A Ge,Linhu %D 2020 %J Frontiers in Oncology %C %F %G English %K oral squamous cell carcinoma,mir-146a,Huntington gene,Migration,invasion,metastasis,tumorigenesis %Q %R 10.3389/fonc.2020.585976 %W %L %M %P %7 %8 2020-November-13 %9 Original Research %+ Janak L. Pathak,Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine,China,gelinhu@yeah.net %+ Janak L. Pathak,Institute of Oral Disease, Guangzhou Medical University,China,gelinhu@yeah.net %+ Linhu Ge,Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine,China,gelinhu@yeah.net %+ Linhu Ge,Institute of Oral Disease, Guangzhou Medical University,China,gelinhu@yeah.net %# %! miR-146a overexpression in oral squamous cell carcinoma %* %< %T miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT %U https://www.frontiersin.org/articles/10.3389/fonc.2020.585976 %V 10 %0 JOURNAL ARTICLE %@ 2234-943X %X 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.