FAM64A promotes HNSCC tumorigenesis by mediating transcriptional autoregulation of FOXM1  

作　　者：Xinyuan Zhao Huan Chen Yu Qiu Li Cui 

机构地区：[1]Stomatological Hospital,Southern Medical University,Guangzhou,China [2]Department of Oral and Maxillofacial Surgery,the First Affiliated Hospital,Fujian Medical University,Fuzhou,China [3]School of Dentistry,University of California,Los Angeles,Los Angeles,CA,USA

出　　处：《International Journal of Oral Science》2022年第3期275-286,共12页国际口腔科学杂志（英文版）

基　　金：supported by National Natural Science Foundation of China(81901006);Guangdong Basic and Applied Basic Research Foundation(2020A1515110051);Scientific Research Talent Cultivation Project of Stomatological Hospital,Southern Medical University(RC202005);Science Research Cultivation Program of Stomatological Hospital,Southern Medical University(PY2020002)。

摘　　要：Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that the expression levels of family with sequence similarity 64,member A(FAM64A)were significantly higher in HNSCC tissues and cell lines.In addition,FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC.Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells,and vice versa.Moreover,we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model.Mechanistically,a physical interaction was found between FAM64A and forkhead box protein M1(FOXM1)in HNSCC cells.FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1,but also,more importantly,by modulating FOXM1 expression via the autoregulation loop.Furthermore,a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts.Taken together,our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC,and FAM64A might be a promising molecular therapeutic target for treating HNSCC.

关 键 词：FAM64A promotes HNSCC tumorigenesis by mediating transcriptional autoregulation of FOXM1 

分 类 号：R739.91[医药卫生—肿瘤]