Email updates

Keep up to date with the latest news and content from BMC Medical Genomics and BioMed Central.

Open Access Highly Accessed Research article

miRNAs associated with chemo-sensitivity in cell lines and in advanced bladder cancer

Iver Nordentoft1*, Karin Birkenkamp-Demtroder1, Mads Agerbæk2, Dan Theodorescu3, Marie Stampe Ostenfeld1, Arndt Hartmann4, Michael Borre5, Torben F Ørntoft1 and Lars Dyrskjøt1

Author Affiliations

1 Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

2 Department of Oncology, Aarhus University Hospital, Aarhus, Denmark

3 University of Colorado Comprehensive Cancer Center, Aurora, CO 80045, USA

4 Department of Pathology, University of Erlangen, Erlangen, Germany

5 Department of Urology, Aarhus University Hospital, Aarhus, Denmark

For all author emails, please log on.

BMC Medical Genomics 2012, 5:40  doi:10.1186/1755-8794-5-40

Published: 6 September 2012

Abstract

Background

MicroRNA is a naturally occurring class of non-coding RNA molecules that mediate posttranscriptional gene regulation and are strongly implicated in cellular processes such as cell proliferation, carcinogenesis, cell survival and apoptosis. Consequently there is increasing focus on miRNA expression as prognostic factors for outcome and chemotherapy response. Only approximately 50% of patients with bladder cancer respond to chemotherapy. Therefore, predictive markers, such as miRNAs, that can identify subgroups of patients who will benefit from chemotherapy will have great value for treatment guidance.

Methods

We profiled the expression of 671 miRNAs in formalin fixed paraffin embedded tumors from patients with advanced bladder cancer treated with cisplatin based chemotherapy. We delineated differentially expressed miRNAs in tumors from patients with complete response vs. patients with progressive disease and in tumors form patients with short and long overall survival time. Furthermore, we studied the effect of up- and down regulation of key miRNAs on the cisplatin sensitivity in eight bladder cancer cell lines with different sensitivities to cisplatin.

Results

miRNA expression profiling identified 15 miRNAs that correlated with response to chemotherapy and 5 miRNAs that correlated with survival time. Three miRNAs were associated with both response and survival (886-3p, 923, 944). By changing the cellular level of the response-identified miRNAs in eight bladder cell lines with different cisplatin sensitivity we found that down-regulation of miR-27a, miR296-5p and miR-642 generally reduced the cell viability, whereas up-regulation of miR-138 and miR-886-3p reduced the viability of more than half of the cell lines. Decreasing miR-138 increased the cisplatin sensitivity in half of the cell lines and increasing miR-27a and miR-642 generally increased cisplatin sensitivity.

Conclusions

MiRNAs seem to be involved in cisplatin based chemo response and may form a new target for therapy and serve as biomarkers for treatment response.