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DNA methylation affects metastasis of renal cancer and is associated with TGF-β/RUNX3 inhibition

Authors :
Guangsheng Zhai
Yanhui Mei
Chuanbing Xu
Ping Xiang
Zhengsheng Pan
Min Liu
Jianbo Zheng
Ning Zhao
Dongsheng Jia
Kai Tang
Source :
Cancer Cell International, Vol 18, Iss 1, Pp 1-11 (2018), Cancer Cell International
Publication Year :
2018
Publisher :
Springer Science and Business Media LLC, 2018.

Abstract

Background Renal cell carcinoma accounts for 2–3% of all cancers and metastasis increased the malignancy of renal cancer. However, the role of methylation in metastasis of renal cancer is poorly understood. Methods We performed targeted gene array to compare the differential expressions of methylation regulated genes in metastatic and primary renal cancer tissues. Quantitative methylation specific PCR was performed to examine the CpG methylation levels of Runt related transcription factor 3 (RUNX3) and transforming growth factor (TGF)-β. Western blot was performed to detect the expression of target genes. Murine xenograft renal cancer model was established to assay gene expression, methylation level, tumor growth and animal survival in vivo. Results RUNX3 and TGF-β levels were decreased in metastatic renal cancer tissues as a result of their CpG methylation. Metastatic xenograft model displayed decreased expression levels of RUNX3 and TGF-β and higher CpG methylation levels, bigger tumor size and shorter survival time, all which were restored by treatment with a methylation inhibitor. Conclusions Hypermethylation in CpG islands promotes metastasis of renal cancer and is associated with TGF-β and RUNX3 inhibition. Electronic supplementary material The online version of this article (10.1186/s12935-018-0554-7) contains supplementary material, which is available to authorized users.

Details

ISSN :
14752867
Volume :
18
Database :
OpenAIRE
Journal :
Cancer Cell International
Accession number :
edsair.doi.dedup.....ba6a53bf25a15226cb34d4c8746f6e9a