Hsa-miR-206 represses the proliferation and invasion of breast cancer cells by targeting Cx43.

Abstract

OBJECTIVE:

Hsa-miR-206, a microRNA, was found to be able to switch subtypes by targeting ER-α in breast cancer. However, there are few studies addressing the role of miR-206 in triple-negative breast cancer (TNBC). The purpose of this study was to evaluate the metastatic-regulatory ability of miR-206 in TNBC.

MATERIALS AND METHODS:

We treated two TNBC lines (MDA-MB-231 and MDA-MB-436) with miR-206 mimics, inhibitors and paired controls and examined the in vitro and in vivo functions of miR-206 via the degradation of Connexin43 (Cx43). A luciferase reporter assay was used to identify the binding site of GJA1 (gap junctional intercellular communication) (Cx43) and miR-206. Furthermore, quantitative RT-PCR was used to evaluate miR-206 expression in 77 breast cancer samples to determine the association with lymph node status and Cx43 expression.

RESULTS:

Up-regulation of miR-206 in TNBC contributed to a decreasing metastatic potential, as demonstrated by a reduction of cell viability and proliferation, decreased cell migration and invasion, lower expression levels of matrix metalloproteinase (MMP)-2, MMP-9 and a higher expression level of breast cancer metastatic suppressor (BRMS)-1. In vitro dual luciferase assays showed GJA1 (Cx43) is a target of miR-206. Quantitative RT-PCR was conducted to evaluate miR-206 expression in 77 breast cancer samples to determine the associations between miR-206 levels and both lymph node status and Cx43 expression. Restoring Cx43 expression positively regulated cell adhesion and GJA1, which may facilitate metastasis. MiR-206 significantly attenuated the proliferation and metastatic potential of cancer cells but did not inhibit tumor onset in a mouse xenograft model because of the dual function of Cx43.

CONCLUSIONS:

Our results suggest hsa-miR-206 may repress the tumor proliferation and invasion in breast cancer by targeting Cx43.

• Authors: Y Fu, Z-M Shao, Q-Z He, B-Q Jiang, Y Wu, Z-G Zhuang
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 19 Issue 11 Pg. 2091-104 ( 2015) ISSN: 2284-0729 [Electronic] Italy
• PMID: 26125274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Connexin 43
• ESR1 protein, human
• Estrogen Receptor alpha
• GJA1 protein, human
• MIRN206 microRNA, human
• MicroRNAs
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Animals
• Base Sequence
• Cell Adhesion
• Cell Line, Tumor
• Cell Proliferation
• Connexin 43 (metabolism)
• Estrogen Receptor alpha (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• MicroRNAs (genetics)
• Neoplasm Metastasis
• Triple Negative Breast Neoplasms (genetics, pathology)
• Up-Regulation