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

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.

MicroRNA-34a Inhibition of the TLR Signaling Pathway Via CXCL10 Suppresses Breast Cancer Cell Invasion and Migration

“…Underlying risk factors for breast cancer include being overweight, alcohol consumption, physical inactivity, nulliparous, recent use of oral contraceptives, and a long menstrual history [2]. Although neoadjuvant and systemic chemotherapy has been widely used to treat breast cancer, successful molecular-targeted therapies of any type are currently unavailable [5]. Recent studies have started to focus on the roles of miR in breast cancer development and progression [6, 7].…”

Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

“…Moreover, Raptor was previously shown to be required for HSC regeneration and its loss led to accumulation of monocytoid cells, pancytopenia, and splenomegaly in mice [63]. Although miR-1246 was previously identified as a regulator of cancer progression, drug resistance [70,71], and a putative biomarker [31,72], our data suggest a role in regulating other tissue compartments, including BM HSC. Thus, our results fit a model of translational suppression by AML-EV miRNA [64] and find support in existing reports of miRNA suppression of protein synthesis [65,66] and Raptor deregulation in hematopoietic cells [67][68][69].…”

The Dysregulated Expression of KCNQ1OT1 and Its Interaction with Downstream Factors miR-145/CCNE2 in Breast Cancer Cells

“…For instance, miR-129-5p was demonstrated to stimulate Her-2-positive breast cancer sensitive to trastuzumab [9]. MiR-212-5p/miR-101 was validated to exert inhibitory influences on breast cancer in some studies [10,11], while miR-1246 promoted breast cancer and its drug resistance, [12] and miR-181a had dual regulatory roles in BRCA [13]. The molecular regulatory network of BRCA is quite complex, and thus, the specific molecular mechanisms of BRCA progression remain to be further elaborated.…”