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Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer

Authors :
Xiu Juan Li
Zhao Jun Ren
Jin Hai Tang
Qiao Yu
Source :
Cellular Physiology and Biochemistry, Vol 44, Iss 5, Pp 1741-1748 (2017)
Publication Year :
2017
Publisher :
Cell Physiol Biochem Press GmbH & Co KG, 2017.

Abstract

Background/Aims: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. Methods: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. Results: In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Conclusions: Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics.

Details

Language :
English
ISSN :
10158987 and 14219778
Volume :
44
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Cellular Physiology and Biochemistry
Publication Type :
Academic Journal
Accession number :
edsdoj.fdae79510a7645198675d4cfd64c4c13
Document Type :
article
Full Text :
https://doi.org/10.1159/000485780