MiRNA-15a Mediates Cell Cycle Arrest and Potentiates Apoptosis in Breast Cancer Cells by Targeting Synuclein-γ

Abstract

Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-γ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.

MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression

“…Increasing evidences indicated that some miRNAs act as either tumor suppressors or promoters in the development of various cancers and play crucial roles in causing messenger RNA (mRNA) degradation or translational inhibition by interacting with the 3′-untranslated region (3′-UTR) of the target mRNA [2][3][4]. Treatment by targeting microRNAs (miRNAs) has attracted extensive research attention in various cancers, including breast cancer [5][6][7][8]. However, the molecular underpinnings of cell proliferation and cell cycle in breast cancer remain incompletely understood.…”

Downregulation of microRNA-497 is associated with upregulation of synuclein γ in patients with osteosarcoma

“…The miR-15 superfamily is located in the 13q14 region of human chromosomes, and includes miR-15a, miR-15b, miR-16, miR-195, miR-424 and miR-497. A previous study revealed that miRNA-15a regulates the cell cycle and apoptosis of breast cancer cells through its target gene, SNCG (16). Using bioinformatic tools, the present study revealed that miR-497 is located within close proximity of miR-15a and possibly participates in the regulation of SNCG.…”

“…Bioinformatics is the predominant method used for the functional analysis of miRNA. A previous study revealed evidence of the regulation of SNCG by one of its upstream mRNAs, miR-15a (16). Using miRanda (www.microrna.org/microrna/getExprForm.do; version 2010), TargetScan (www.targetscan.org/vert_61; version 6.2), PieTar (www.pictar.mdc-berlin.de; version 2007) and BibiServ (www.bibiserv.techfak.uni-bielefield.be/bibi/ Tools.html; version 2013) databases, the miR-15 family genes were screened (miR-15a, miR-15b, miR-16, miR-195, miR-424 and miR-497), and miR-497 was selected for evaluation in the present study, due to it having similar SNCG-binding sites to miR-15a (Fig.…”

Long non-coding RNA AK058003, as a precursor of miR-15a, interacts with HuR to inhibit the expression of γ-synuclein in hepatocellular carcinoma cells

“…StarBase2.0 was used to predict and select miRNAs that interacted with the SNCG (Supplementary Table S1). Among these miRNA candidates, we found that miR-15a directly binds to the SNCG [24]. We performed bioinformatics analysis to identify the homologous sequences of lncRNA-AK058003, HuR and miR-15a.…”