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Open Access Highly Accessed Research article

Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells

Chandrani Achari, Sofia Winslow, Yvonne Ceder and Christer Larsson*

Author Affiliations

Department of Laboratory Medicine, Translational Cancer Research, Lund University, Medicon Village, Building 404:C3, 223 81 Lund, Sweden

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BMC Cancer 2014, 14:538  doi:10.1186/1471-2407-14-538

Published: 26 July 2014

Abstract

Background

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. Here, we examine functions of miR-34c in basal-like breast cancer cells.

Methods

Data 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.

Results

TCGA 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.

Conclusions

Together, our results support the role of miR-34c as a tumor suppressor miRNA also in breast cancer.

Keywords:
Breast cancer cells; miRNA-34c; CDC23; PKCĪ±; Cell cycle arrest