Open AccessTreatment with an SLC12A1 antagonist inhibits tumorigenesis in a subset of hepatocellular carcinomas
Author(s) -
Fei Teng,
Meng Guo,
Fang Liu,
Ce Wang,
Jia-yong Dong,
Lei Zhang,
You Zou,
Rui Chen,
Ke-Yan Sun,
Hong Fang,
Zhi-ren Fu,
Weijian Guo,
Guoyu Ding
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.10670
Subject(s) - cancer research , carcinogenesis , hepatocellular carcinoma , hccs , downregulation and upregulation , biology , medicine , cancer , microarray , gene expression , gene , genetics
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.