Zheng Jianbo, Mei Yanhui, Xiang Ping, Zhai Guangsheng, Zhao Ning, Xu Chuanbing, Liu Min, Pan Zhengsheng, Tang Kai, Jia Dongsheng
1Department of Urology, QiLu Hospital of Shandong University, 107 Wenhua Western Road, Jinan, 250012 Shandong Province China.
2Department of Urology, Central Hospital of Zibo, No. 54 Gongqingtuan West Road, Zhangdian District, Zibo, 255036 Shandong Province China.
Cancer Cell Int. 2018 Apr 10;18:56. doi: 10.1186/s12935-018-0554-7. eCollection 2018.
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.
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.
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.
Hypermethylation in CpG islands promotes metastasis of renal cancer and is associated with TGF-β and RUNX3 inhibition.
肾细胞癌占所有癌症的2%-3%，转移会增加肾癌的恶性程度。然而，甲基化在肾癌转移中的作用尚不清楚。
我们进行了靶向基因芯片分析，以比较转移性和原发性肾癌组织中甲基化调控基因的差异表达。采用定量甲基化特异性PCR检测 runt 相关转录因子3（RUNX3）和转化生长因子（TGF）-β的 CpG 甲基化水平。通过蛋白质印迹法检测靶基因的表达。建立小鼠异种移植肾癌模型，以检测体内基因表达、甲基化水平、肿瘤生长和动物存活情况。
由于 CpG 甲基化，转移性肾癌组织中 RUNX3 和 TGF-β水平降低。转移性异种移植模型显示 RUNX3 和 TGF-β表达水平降低，CpG 甲基化水平升高，肿瘤体积增大，生存时间缩短，而用甲基化抑制剂治疗可恢复所有这些情况。
CpG 岛的高甲基化促进肾癌转移，并与 TGF-β和 RUNX3 抑制有关。
