Histone demethylase JARID1C promotes breast cancer metastasis cells via down regulating BRMS1 expression

Metastasis is the leading cause of death in breast cancer patients. However, until now, the mechanisms of breast cancer metastasis remain elusive. Epigenetic switch, including histone methylation or demethylation, which can either activates or represses transcription. The JARID1C is a histone demethylase that promotes cancer cell growth and is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation. But the pathogenic breadth and mechanistic aspects of this effect relative to breast cancer have not been defined. In this study, we aimed to investigate the role of JARID1C in breast cancer. In clinical breast cancer samples, we found that JARID1C expression was significantly upregulated in cancer lesions compared with paired normal breast tissues and its expression level is positively correlated with metastasis. Silencing JARID1C in breast cancer cells could inhibit cell migration and invasion. Moreover, we also found that the expression of BRMS1 was modulated by JARID1C. Silencing of JARID1C dramatically increased BRMS1 expression both at mRNA and protein level. Mechanistically, we found JARID1C exerts its function through modulation of H3K4me3 at the BRMS1 gene promoter, which was associated with inactive BRMS1 transcription. BRMS1 knockdown reversed shJARID1C-induced migration inhibition. Further, BRMS1 expression in human breast cancer is negatively correlated with JARID1C expression. Our results, for the first time, portray a pivotal role of JARID1C in regulating metastatic behaviors of breast cancer cells.