Y Fu1, Z-M Shao, Q-Z He, B-Q Jiang, Y Wu, Z-G Zhuang. 1. Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China. zhuang_zg@163.com.
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.
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: Chi Pang; Gang Huang; Kaili Luo; Yuying Dong; Fengtian He; Guankui Du; Man Xiao; Wangwei Cai Journal: Cancer Med Date: 2017-09-21 Impact factor: 4.452