Open Access

ARTICLE

Decreased invasion ability of hypotaurine synthesis deficient glioma cells was partially due to hypomethylation of Wnt5a promoter

Hong TIAN^{1, 2}, Peiyu CONG³, Ruiqun QI⁴, Xinghua GAO⁵, Xin LIU⁶, Hongsheng LIU⁷, Fengping SHAN^1,*

1 Department of Immunology, School of Basic Medical Science, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, P.R. China
2 Oncology Department, The 4th People’s Hospital of Shenyang, 20 Huanghe South Street, Shengyang, Liaoning, 110122, P.R. China
3 Department of neurosurgery, Dalian Municipal Central Hospital, 826 Xinan Road, Dalian, Liaoning, 116023, P.R. China
4 Department of Dermatology, Key Laboratory of Immunodermatology No.1 Hospital of China Medical University, 155 Nanjing Road, Heping District, Shenyang, Liaoning, 110001, P.R. China
5 Department of Dermatology, No.1 Hospital of China Medical University, 92 North Second Road, Heping District, Shenyang, Liaoning, 110001, P.R. China
6 The First Affiliated Hospital of Jinzhou Medical University, 2 Wuduan Renmin Street, Jinzhou, Liaoning, 121001 P.R. China
7 Heart ICU, Affiliated Hospital of Jining Medical College, 79 Guhuai Road, Jining, Shangdong, 272000, P.R. China

* Address correspondence to: Fengping Shan,

BIOCELL 2017, 41(1), 27-32. https://doi.org/10.32604/biocell.2017.41.027

Abstract

Glioma is one of the lethal central nervous system tumors. The infiltrative and invasive growth nature makes it difficult to identify the boundary between glioma and the normal tissues, resulting in inevitable recurrence after surgery operation. Gliomas do not metastasize, so to prevent the residual tumor from proliferating or invading is a key challenge. Previous report indicated that hypotaurine could facilitate glioma invasion and suppress demethylases’ activities. Using a hypotaurine synthesis deficient U251 cell line, we proved that the cells invasion ability was impaired. Gene expression profile analysis exhibited that knocking down one of the key enzymes of hypotaurine synthesis, 2-aminoethanethiol dioxygenase (ADO), significantly affected the extracellular matrix-receptor process. Of that process, Wnt5a expression was severely upregulated by decreased intracellular ADO expression. Cells cultured at the presence of hypotaurine showed a decrease in intracellular Wnt5a protein and mRNA levels. This phenotype was due to hypermethylation of Wnt5a promoter, which was most likely the result of hypotaurine’s inhibiting demethylases activities. Collectively, this study demonstrated that hypotaurine synthesis deficient U251 cells were prone to epigenetic modification and Wnt5a seemed to be a tumor suppressor under that circumstance. This tumor suppression effect is warranted to be reevaluated in real tumor samples and the relevant evidence might contribute to develop new glioma interference strategies.

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