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DNA methylation affects metastasis of renal cancer and is associated with TGF-β/RUNX3 inhibition
- 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.
- Subjects :
- TGF-β
0301 basic medicine
Cancer Research
RUNX3
Xenograft model
Bisulfite sequencing
Biology
Methylation
lcsh:RC254-282
Metastasis
03 medical and health sciences
0302 clinical medicine
Renal cell carcinoma
CpG
Gene expression
Genetics
medicine
lcsh:QH573-671
lcsh:Cytology
Cancer
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Renal cancer
030104 developmental biology
Oncology
CpG site
030220 oncology & carcinogenesis
DNA methylation
Cancer research
Primary Research
Subjects
Details
- ISSN :
- 14752867
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Cancer Cell International
- Accession number :
- edsair.doi.dedup.....ba6a53bf25a15226cb34d4c8746f6e9a