Med19 is targeted by miR-101–3p/miR-422a and promotes breast cancer progression by regulating the EGFR/MEK/ERK signaling pathway

• Published in: Cancer letters 2019-03, Vol.444, p.105-115
• Main Authors: Zhang, Xiufen, Gao, Danfeng, Fang, Kai, Guo, Zijian, Li, Lihua
• Format: Article
• Language: English
• Subjects: Breast cancer; Cancer therapies; Cell cycle; Cell growth; Cell proliferation; Colorectal cancer; Epidermal growth factor; Epidermal growth factor receptors; Epithelial-mesenchymal transition; Extracellular signal-regulated kinase; Gene expression; Invasion; Kinases; Laboratory animals; MAP kinase; Mesenchyme; Metabolic pathways; Metastasis; Migration; Protein kinase; Proteins; Signal transduction; Tissues; Tumorigenesis; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2018.12.008

Our previous study found that mediator complex subunit 19 (Med19) is upregulated and involved in breast cancer tumorigenesis; however, the detailed effects and mechanism of Med19 in breast cancer require further study. In this study, we found that Med19 was obviously elevated in human breast cancer tissues, which was significantly associated with larger tumors, high-grade malignant features and poor prognosis. Furthermore, Med19 enhanced breast cancer cell proliferation, epithelial–mesenchymal transition, invasion and migration in vitro and in vivo. Med19 interacted with epidermal growth factor receptor (EGFR) and increased EGFR expression. Moreover, Med19 activated the EGFR/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway and exerted its oncogenic activity in an EGFR signaling-mediated manner. In addition, Med19 expression was regulated by miR-101–3p and miR-422a. Med19 expression positively correlated with EGFR expression and negatively correlated with miR-101–3p and miR-422a expression in human breast cancer tissues. Med19 mediated the crosstalk between miR-101–3p/miR-422a and the EGFR/MEK/ERK signaling pathway. This study revealed a new miR-101–3p/miR-422a-Med19-EGFR/MEK/ERK axis that plays a significant role in breast cancer progression. These results help elucidate the potential mechanisms of Med19 in human breast cancer progression. •Mediator complex subunit 19 (Med19) was elevated in breast cancer and predicted a poor prognosis for breast cancer patients.•Med19 enhanced breast cancer cell proliferation, epithelial–mesenchymal transition, invasion and migration.•Med19 was targeted by microRNA-101–3p/microRNA-422a and exerted oncogenic activity in an EGFR-mediated manner.•Therapeutic inhibition of Med19 expression could hinder breast cancer growth and metastasis.