Research Papers:

Treatment with an SLC12A1 antagonist inhibits tumorigenesis in a subset of hepatocellular carcinomas

Fei Teng _, Meng Guo, Fang Liu, Ce Wang, Jiayong Dong, Lei Zhang, You Zou, Rui Chen, Keyan Sun, Hong Fu, Zhiren Fu, Wenyuan Guo and Guoshan Ding

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Oncotarget. 2016; 7:53571-53582. https://doi.org/10.18632/oncotarget.10670

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Fei Teng1,*, Meng Guo1,*, Fang Liu1,*, Ce Wang2, Jiayong Dong1, Lei Zhang1, You Zou1, Rui Chen1, Keyan Sun1, Hong Fu1, Zhiren Fu1, Wenyuan Guo1, Guoshan Ding1

1Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China

2Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China

*These authors have contributed equally to this work

Correspondence to:

Guoshan Ding, email: dingguoshanmail@163.com

Wenyuan Guo, email: gwyuan7502@aliyun.com

Keywords: HCC, liver cancer, SLC12A1, cancer outlier profile analysis, Bumetanide

Received: October 02, 2015    Accepted: July 06, 2016    Published: July 18, 2016


A central aim in cancer research is to identify genes with altered expression patterns in tumor specimens and their potential role in tumorigenesis. Most types of tumors, including hepatocellular carcinoma (HCC), are heterogeneous in terms of genotype and phenotype. Thus, traditional analytical methods like the t-test fail to identify all oncogenes from expression profiles. In this study, we performed a meta-Cancer Outlier Profile Analysis (meta-COPA) across six microarray datasets for HCC from the GEO database. We found that gene SLC12A1 was overexpressed in the Hep3B cell line, compared with five other HCC cell lines and L02 cells. We also found that the upregulation of SLC12A1 was mediated by histone methylation within its promoter region, and that SLC12A1 is a positive regulator of the WNK1/ERK5 pathway. Consistent with in vitro results, treatment with the SLC12A1 antagonist Bumetanide delayed tumor formation and reduced Hep3B cell tumor size in mouse xenografts. In summary, our research reveals a novel subset of HCCs that are sensitive to SLC12A1 antagonist treatment, thereby offering a new strategy for precision HCC treatment.

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