Abstract
BackgroundMicroRNA-34 is a family of three miRNAs that have been reported to function as tumor suppressor miRNAs and show decreased expression in various cancers. Here, we examine functions of miR-34c in basal-like breast cancer cells.MethodsData from The Cancer Genome Atlas (TCGA) were used for evaluation of expression in primary breast cancers. Cellular processes affected by miR-34c were investigated by thymidine incorporation, Annexin V-assays and cell cycle analysis using breast cancer cell lines. Effects on potential targets were analyzed with qPCR and Western blot.ResultsTCGA data revealed that miR-34c was expressed at lower levels in basal-like breast cancer tumors and low expression was associated with poor prognosis. Ectopic expression of miR-34c in basal-like breast cancer cell lines resulted in suppressed proliferation and increased cell death. Additionally, miR-34c influenced the cell cycle mainly by inducing an arrest in the G2/M phase. We found that expression levels of the known cell cycle-regulating miR-34 targets CCND1, CDK4 and CDK6, were downregulated upon miR-34c expression in breast cancer cell lines. In addition, the levels of CDC23, an important mediator in mitotic progression, were suppressed following miR-34c expression, and siRNAs targeting CDC23 mimicked the effect of miR-34c on G2/M arrest. However, protein levels of PRKCA, a predicted miR-34c target and a known regulator of breast cancer cell proliferation were not influenced by miR-34c.ConclusionsTogether, our results support the role of miR-34c as a tumor suppressor miRNA also in breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-538) contains supplementary material, which is available to authorized users.
Highlights
MicroRNA-34 is a family of three miRNAs that have been reported to function as tumor suppressor miRNAs and show decreased expression in various cancers
We found that miR-34c overexpression both blocks the proliferation of cultured basal-like breast cancer cells and induces cell death, this was not mediated by PKCα downregulation
We found that miR-34c overexpression resulted in decreased protein levels of cyclin D1, Cyclin-dependent kinase 4 (CDK4) and Cyclin-dependent kinase 6 (CDK6) in all cell lines (Figure 5A)
Summary
MicroRNA-34 is a family of three miRNAs that have been reported to function as tumor suppressor miRNAs and show decreased expression in various cancers. We examine functions of miR-34c in basal-like breast cancer cells. MicroRNAs (miRNAs) are small (~22 nt) non-coding RNAs of importance for protein level regulation. They act by interacting with the 3’UTR of the target mRNA which may cause mRNA degradation or translational inhibition [1,2]. A recent study with prostate cancer PC3 cells revealed that miR-34c expression resulted in downregulation of protein kinase Cα (PKCα) mRNA [21]. From a breast cancer perspective this could be of relevance since PKCα expression has been reported to be important for optimal breast cancer cell proliferation [28,29], support a cancer stem cell-like breast cancer cell population [30] and to predict poorer survival [28]
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