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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Nuclear Receptor Coactivator 2 Promotes Human Breast Cancer Cell Growth by Positively Regulating the MAPK/ERK Pathway
Mengjiao Cai1,2, Xin Liang2,3, Xiao Sun1,2
1Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Abstract:
As a member of the p160 steroid receptor coactivator (SRC) family, nuclear receptor coactivator 2 (NCOA2) is known to play essential roles in many physiological and pathological processes, including development, endocrine regulation, and tumorigenesis. However, the biological function of NCOA2 in breast cancer is not fully understood. We found that the copy number of the NCOA2 gene was frequently amplified in four breast cancers datasets, varying from 6 to 10%, and the mRNA levels of NCOA2 were also upregulated in 11% of the sequenced cases/patients (TCGA provisional dataset). Next, we confirmed that NCOA2 silencing significantly suppressed cell proliferation in different breast cancer cell lines, by inducing cell cycle arrest and apoptosis. Mechanistically, whole-transcriptome sequencing (RNA-Seq) analysis showed that NCOA2 depletion leads to downregulation of the MAPK/ERK signaling cascade, possibly via downregulating NCOA2's downstream target RASEF. In conclusion, our results suggest NCOA2 as a potential target of therapeutics against breast cancer.
Insights
Nuclear receptor coactivator 2 (NCOA2) amplification and upregulation promote breast cancer growth. Silencing NCOA2 inhibits proliferation by affecting cell cycle and apoptosis, suggesting NCOA2 as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Nuclear receptor coactivator 2 (NCOA2), part of the p160 steroid receptor coactivator (SRC) family, is involved in various physiological and pathological processes.
- The specific role of NCOA2 in breast cancer progression and its underlying mechanisms remain incompletely understood.
Purpose of the Study:
- To investigate the role of NCOA2 in breast cancer.
- To determine the potential of NCOA2 as a therapeutic target for breast cancer.
Main Methods:
- Analysis of NCOA2 gene copy number and mRNA levels in breast cancer datasets (TCGA).
- Experimental manipulation of NCOA2 expression (silencing) in breast cancer cell lines.
- Assessment of cell proliferation, cell cycle, and apoptosis.
- Whole-transcriptome sequencing (RNA-Seq) to identify downstream signaling pathways.
Main Results:
- NCOA2 gene amplification (6-10%) and mRNA upregulation (11%) were observed in breast cancer.
- NCOA2 silencing significantly suppressed breast cancer cell proliferation by inducing cell cycle arrest and apoptosis.
- NCOA2 depletion led to the downregulation of the MAPK/ERK signaling pathway, potentially through its target RASEF.
Conclusions:
- NCOA2 plays a significant role in promoting breast cancer cell proliferation.
- NCOA2 acts through the MAPK/ERK signaling cascade.
- NCOA2 represents a promising therapeutic target for breast cancer treatment.
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