Expression of transmembrane protein 106A(TMEM106A)has been reported to be dysregulated in several types of cancers.However,the role of TMEM106A in hepatocellular carcinoma(HCC)is still unknown.In the present study,we demonstrate that TMEM106A is markedly downregulated in HCC compared with normal liver tissue.In parti-cular,tumor-specific DNA methylation of TMEM106A is frequently observed in tumor tissues from HCC patients.Immunohistochemistry and pyrosequencing reveal a significant relationship between TMEM106A methylation and downregulation of protein expression.Receiver operating characteristic(ROC)curve analysis reveals that methy-lation of TMEM106A in tumor samples is different from that in non-malignant adjacent tissues of HCC patients.Moreover,HCC patients with TMEM106A hypermethylation have a poor clinical prognosis.5-Aza-2'-deoxycytidin treatment of hypermethylated TMEM106A in highly metastatic HCC cells increases the expression of TMEM106A.Functional assays reveal that overexpression of TMEM106A significantly suppresses the malignant behavior of HCC cells in vitro and decreases tumorigenicity and lung metastasis in vivo.Mechanistically,TMEM106A inhibits epi-thelial mesenchymal transition(EMT)of HCC cells through inactivation of the Erk1/2/Slug signaling pathway.In conclusion,our findings demonstrate that TMEM106A is an inhibitor of HCC EMT and metastasis,and TMEM106A is often transcriptionally downregulated by promoter methylation,which results in reduced levels of TMEM106A protein and predicts poor survival outcomes for HCC patients.

Shiming Shi;Biao Wang;Jinglei Wan;Lina Song;Guiqi Zhu;Junxian Du;Luxi Ye;Qianqian Zhao;Jialiang Cai;Qing Chen;Kun Xiao;Jian He;Lei Yu;Zhi Dai

Liver Cancer Institute,Zhongshan Hospital,Fudan University&State Key Laboratory of Genetic Engineering,Fudan University,Shanghai 200032,China;Department of Radiation Oncology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Pediatric Surgery,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China;Department of General Surgery,Zhongshan Hospital(South),Fudan University,Shanghai Public Health Clinical Center,Fudan University,Shanghai 200083,China;Department of Gastrointestinal Surgery,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,China;Department of Liver Surgery and Transplantation,Liver Cancer Institute,Zhongshan Hospital,Fudan University,Shanghai 200032,China

生物化学与生物物理学报（英文版）

[1]Shiming Shi;Biao Wang;Jinglei Wan;Lina Song;Guiqi Zhu;Junxian Du;Luxi Ye;Qianqian Zhao;Jialiang Cai;Qing Chen;Kun Xiao;Jian He;Lei Yu;Zhi Dai-.TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma)[J].生物化学与生物物理学报（英文版）,2022(07):1008-1020

TMEM106A,106A,deoxycytidin

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