1. Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer
- Author
-
Qiao Yu, Zhao Jun Ren, Xiu Juan Li, and Jin Hai Tang
- Subjects
0301 basic medicine ,Physiology ,Cyclin G2 ,Breast Neoplasms ,Biology ,Exosomes ,lcsh:Physiology ,lcsh:Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Gentamicin protection assay ,Cell Movement ,Cell Line, Tumor ,RNA, Small Nuclear ,microRNA ,medicine ,Cluster Analysis ,Humans ,lcsh:QD415-436 ,Viability assay ,3' Untranslated Regions ,miR-1246 ,Cell Proliferation ,Oligonucleotide Array Sequence Analysis ,Base Sequence ,lcsh:QP1-981 ,Cell growth ,medicine.disease ,Metastatic breast cancer ,CCNG2 ,Microvesicles ,Up-Regulation ,MicroRNAs ,030104 developmental biology ,Real-time polymerase chain reaction ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,MCF-7 Cells ,Female ,Sequence Alignment - 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.
- Published
- 2017