J Cancer 2019; 10(21):5256-5263. doi:10.7150/jca.30098
Hypermethylation of BRM promoter plays oncogenic roles in development of clear cell renal cell carcinoma
1. Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, Jiangsu, China
2. Center for Health Management, Geriatric Hospital of Nanjing Medical University, Nanjing, 210009, China;
3. Department of Medical Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
4. Sir Run Run Shaw Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, China.
*These authors contributed equally to this work
Although the inactivation of BRM plays oncogenic roles in tumorigenesis, regulation mechanism is rarely studied in clear cell renal cell carcinoma (RCC). Thus, we aimed to investigate the mechanism of BRM inactivation and explore the tumor suppressing roles of BRM in the development of clear cell RCC. We verified that hypermethylation of the BRM promoter was correlated with decreased expression of BRM by multi-omics analysis based on the TCGA database. This result was further confirmed in our own tumor tissues. Moreover, BRM inhibited the ability of proliferation and invasion of RCC cells in vitro. Consistent with this, BRM overexpressing virtually inhibited the xenograft tumor growth of ACHN cells in vivo. Finally we found that BRM promoted cell apoptosis and cellular cycle arrest in G2/M. In conclusion, our study confirms that the hypermethylation of BRM promoters plays oncogenic roles by the transcription inhibition of BRM in RCC, and the tumor suppressor gene BRM inhibits RCC cell vitality in vitro and in vivo.
Keywords: BRM, clear cell renal cell carcinoma, methylation, copy number variation, proliferation, apoptosis.
Fang R, Xia Q, Sun J, ng HZ, Liang Y, Wang X, Wang X, Ma H, Zhou X, Cheng Y, Rao Q. Hypermethylation of BRM promoter plays oncogenic roles in development of clear cell renal cell carcinoma. J Cancer 2019; 10(21):5256-5263. doi:10.7150/jca.30098. Available from http://www.jcancer.org/v10p5256.htm