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

Cancer Cell International

Guangsheng Zhai¹  Ping Xiang²  Yanhui Mei³  Min Liu⁴  Ning Zhao⁴  Dongsheng Jia⁴  Chuanbing Xu⁴  Zhengsheng Pan⁴  Kai Tang⁴  Jianbo Zheng⁵ 

[1] Department of Radiotherapy, Central Hospital of Zibo;Department of Urology, Anhui Provincial Hospital;Department of Urology, Binzhou Medical University Hospital;Department of Urology, Central Hospital of Zibo;Department of Urology, QiLu Hospital of Shandong University;

关键词: Renal cancer;    Methylation;    RUNX3;    TGF-β;    Metastasis;    CpG;   

DOI  :  10.1186/s12935-018-0554-7

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown