Identification of Methylation-Driven, Differentially Expressed STXBP6 as a Novel Biomarker in Lung Adenocarcinoma

被引:20
作者
Lenka, Govinda [1 ]
Tsai, Mong-Hsun [2 ,3 ]
Lin, Hsin-Chieh [1 ]
Hsiao, Jen-Hao [4 ]
Lee, Yi-Ching [5 ]
Lu, Tzu-Pin [6 ]
Lee, Jang-Ming [7 ]
Hsu, Chung-Ping [8 ]
Lai, Liang-Chuan [1 ,3 ]
Chuang, Eric Y. [3 ,4 ,9 ]
机构
[1] Natl Taiwan Univ, Grad Inst Physiol, Taipei, Taiwan
[2] Natl Taiwan Univ, Inst Biotechnol, Taipei, Taiwan
[3] Natl Taiwan Univ, Ctr Genom Med, Bioinformat & Biostat Core, Taipei, Taiwan
[4] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei, Taiwan
[5] Acad Sinica, Inst Cellular & Organism Biol, Taipei, Taiwan
[6] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Dept Publ Hlth, Taipei, Taiwan
[7] Natl Taiwan Univ Hosp, Dept Surg, Taipei, Taiwan
[8] Taichung Vet Gen Hosp, Div Thorac Surg, Taichung, Taiwan
[9] China Med Univ, Sch Chinese Med, Taichung, Taiwan
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词
DNA METHYLATION; GENE-EXPRESSION; PROMOTER METHYLATION; MESSENGER-RNA; CANCER; VALIDATION; SIGNATURE; GENOME; AMISYN; SECRETION;
D O I
10.1038/srep42573
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
DNA methylation is an essential epigenetic marker associated with the silencing of gene expression. Although various genome-wide studies revealed aberrantly methylated gene targets as molecular biomarkers for early detection, the survival rate of lung cancer patients is still poor. In order to identify methylation-driven biomarkers, genome-wide changes in DNA methylation and differential expression in 32 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined. This concurrent analysis identified 21 negatively correlated probes (r = -0.5), corresponding to 17 genes. Examining the endogenous expression in lung cancer cell lines, five of the genes were found to be significantly down-regulated. Furthermore, in tumor cells alone, 5-aza-2'-deoxycytidine treatment increased the expression levels of STXBP6 in a dose dependent manner and pyrosequencing showed higher percentage of methylation in STXBP6 promoter. Functional analysis revealed that overexpressed STXBP6 in A549 and H1299 cells significantly decreased cell proliferation, colony formation, and migration, and increased apoptosis. Finally, significantly lower survival rates (P < 0.05) were observed when expression levels of STXBP6 were low. Our results provide a basis for the genetic etiology of lung adenocarcinoma by demonstrating the possible role of hypermethylation of STXBP6 in poor clinical outcomes in lung cancer patients.
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页数:13
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