首页|Upregulation of TMCO3 Promoting Tumor Progression and Contributing to the Poor Prognosis of Hepatocellular Carcinoma

Upregulation of TMCO3 Promoting Tumor Progression and Contributing to the Poor Prognosis of Hepatocellular Carcinoma

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Background and Aims: TMCO3, a member of the monova-lent cation:proton antiporter-2 family, has been annotated as a Na+/H+ antiporter, but its pathophysiological role is still unclear. We aimed to investigate the expression pro-file, prognostic significance, and oncogenic role of TMCO3 in hepatocellular carcinoma (HCC). Methods: Bioinformatic analyses were conducted using transcriptome data from pub-lic databases to determine the expression, prognosis, and functional enrichment of TMCO3 in HCC. TMCO3 expression was further validated in an independent HCC cohort from our institution. The oncogenic role of TMCO3 in HCC was evaluated using in vitro and in vivo experiments. Results: The upregulated expression of TMCO3 was identified and verified in multiple HCC cohorts, and worse overall survival and recurrence-free survival were observed in patients with high TMCO3 expression. The overexpression and knockdown of TMCO3 could affect the proliferation and metastasis of HCC cells, which might be associated with the p53-induced cell cycle regulation and epithelial-mesenchymal transition, respectively. Notably, significant correlations were found be- tween dysregulated TMCO3 and various antitumor agents. Its role in sorafenib sensitivity was further identified by in vitro experiments and the potential mechanism might be related to the regulation of apoptosis. Positive correlations were also identified between upregulation of TMCO3 and the increased infiltration of various immune cells and the elevated expression of multiple immune checkpoint genes in HCC. Conclusions: Upregulated TMCO3 could act as an on- cogenic mediator and promote sorafenib resistance in HCC, providing a potential therapeutic target for HCC treatment.

Hepatocellular carcinomaTMCO3SorafenibOncogene,progno-sis

Tianxing Dai、Linsen Ye、Mingbin Deng、Guozhen Lin、Rongqiang Liu、Haoyuan Yu、Wei Liu、Yang Yang、Guoying Wang

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Department of Hepatic Surgery and Liver Transplant Program,The Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou,Guangdong,China

Guangdong Key Laboratory of Liver Disease Research,The Third Affiliated Hospital ofSun Yat-Sen University,Guangzhou,Guangdong,China

Department of Hepatic Surgery,The Third People's Hospital of Shenzhen,Shenzhen,Guangdong,China

Department of Hepatobiliary Surgery,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong,China

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广东省自然科学基金广东省自然科学基金Guangdong Key Laboratory of Liver Disease Research国家自然科学基金国家自然科学基金

2015A0303130382015A0303120132017B0303140278177064881972286

2022

10.14218/JCTH.2021.00346

临床与转化肝病杂志(英文版)

临床与转化肝病杂志(英文版)

ISSN：
年,卷(期)：2022.10(5)
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