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Histone demethylase JARID1C promotes breast cancer metastasis cells via down regulating BRMS1 expression
Qin Wang1, Junmin Wei2, Peng Su3
1Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, PR China.
Abstract:
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.
Insights
JARID1C, a histone demethylase, is upregulated in breast cancer and promotes metastasis. Inhibiting JARID1C reduces cancer cell migration and invasion by increasing BRMS1 expression, offering a potential therapeutic target.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Metastasis is the primary cause of mortality in breast cancer patients.
- The precise mechanisms driving breast cancer metastasis are not fully understood.
- JARID1C, a histone demethylase, influences gene transcription and chromatin remodeling, and is linked to cancer cell proliferation.
Purpose of the Study:
- To investigate the role of JARID1C in breast cancer progression and metastasis.
- To elucidate the molecular mechanisms by which JARID1C affects breast cancer cell behavior.
Main Methods:
- Analysis of JARID1C expression in clinical breast cancer samples.
- In vitro experiments involving silencing JARID1C in breast cancer cells.
- Assessment of cell migration and invasion.
- Quantitative analysis of BRMS1 mRNA and protein levels.
- Chromatin immunoprecipitation to examine histone modifications at the BRMS1 promoter.
Main Results:
- JARID1C expression is significantly elevated in breast cancer tissues compared to normal tissues and correlates positively with metastatic potential.
- Silencing JARID1C inhibits breast cancer cell migration and invasion.
- JARID1C regulates BRMS1 expression, with JARID1C knockdown leading to increased BRMS1 levels.
- JARID1C functions by modulating H3K4me3 at the BRMS1 promoter, suppressing its transcription.
- BRMS1 knockdown counteracts the inhibitory effects of JARID1C silencing on cell migration.
Conclusions:
- JARID1C plays a critical role in promoting breast cancer metastasis.
- JARID1C's mechanism involves the epigenetic regulation of BRMS1 expression.
- Targeting JARID1C may offer a novel therapeutic strategy for inhibiting breast cancer metastasis.
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