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

Abstract

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.

• Authors: Xiufen Zhang, Danfeng Gao, Kai Fang, Zijian Guo, Lihua Li
• Journal: Cancer letters (Cancer Lett) Vol. 444 Pg. 105-115 (03 01 2019) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 30583076 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers, Tumor
• MED19 protein, human
• MIRN101 microRNA, human
• MIRN422 microRNA, human
• Mediator Complex
• MicroRNAs
• EGFR protein, human
• ErbB Receptors
• MAP Kinase Kinase 1
• MAP2K1 protein, human

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Proliferation
• ErbB Receptors (genetics, metabolism)
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Humans
• MAP Kinase Kinase 1 (genetics, metabolism)
• MAP Kinase Signaling System
• Mediator Complex (genetics, metabolism)
• Mice
• Mice, SCID
• MicroRNAs (genetics)
• Middle Aged
• Prognosis
• Survival Rate
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays