Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer

Clinical Epigenetics

Isik G. Yulug¹  Onder Bozdogan²  Betul Bozkurt³  Ozlen Konu¹  Gurbet Karahan¹  Nilufer Sayar¹ 

[1] Department of Molecular Biology and Genetics, Bilkent University, Faculty of Science, Ankara, TR-06800, Turkey;Department of Pathology, Ankara Numune Training and Research Hospital, Ankara, 06100, Turkey;Department of General Surgery, Ankara Numune Training and Research Hospital, Ankara, 06100, Turkey

关键词: Diagnosis;    Prognosis;    SM22 alpha;    TAGLN;    Breast cancer;    Hypermethylation;    DNA methylation;   

Others  :  1230684
DOI  :  10.1186/s13148-015-0138-5

 received in 2015-07-26, accepted in 2015-09-18,  发布年份 2015

【 摘 要 】

Background

CpG hypermethylation in gene promoters is a frequent mechanism of tumor suppressor gene silencing in various types of cancers. It usually occurs at early steps of cancer progression and can be detected easily, giving rise to development of promising biomarkers for both detection and progression of cancer, including breast cancer. 5-aza-2′-deoxycytidine (AZA) is a DNA demethylating and anti-cancer agent resulting in induction of genes suppressed via DNA hypermethylation.

Results

Using microarray expression profiling of AZA- or DMSO-treated breast cancer and non-tumorigenic breast (NTB) cells, we identified for the first time TAGLN gene as a target of DNA hypermethylation in breast cancer. TAGLN expression was significantly and frequently downregulated via promoter DNA hypermethylation in breast cancer cells compared to NTB cells, and also in 13/21 (61.9 %) of breast tumors compared to matched normal tissues. Analyses of public microarray methylation data showed that TAGLN was also hypermethylated in 63.02 % of tumors compared to normal tissues; relapse-free survival of patients was worse with higher TAGLN methylation; and methylation levels could discriminate between tumors and healthy tissues with 83.14 % sensitivity and 100 % specificity. Additionally, qRT-PCR and immunohistochemistry experiments showed that TAGLN expression was significantly downregulated in two more independent sets of breast tumors compared to normal tissues and was lower in tumors with poor prognosis. Colony formation was increased in TAGLN silenced NTB cells, while decreased in overexpressing BC cells.

Conclusions

TAGLN gene is frequently downregulated by DNA hypermethylation, and TAGLN promoter methylation profiles could serve as a future diagnostic biomarker, with possible clinical impact regarding the prognosis in breast cancer.

【 授权许可】

   
2015 Sayar et al.

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