Abstract
Background:MicroRNAs (miRNAs) are important regulators of cellular processes and are found to be deregulated in many cancers. We here analysed the miRNA expression in anal carcinomas. In a previous study, we found that our anal carcinoma tumours were divided into two groups based on the expression of E2F-regulated genes. Therefore, we searched for miRNAs that could reproduce this grouping.Methods:A global screen of the miRNA population was performed using real-time quantitative PCR (RT–qPCR) array methods and differentially expressed miRNAs were identified. Real-time–qPCR was used to verify the expression levels of selected miRNAs and genes in a larger collection of biopsies. A siRNA-mediated knockdown of human papilloma virus (HPV)16 E7 in a cervical cell line was performed to assess the effect of E7 on miR-15b.Results:The grouping of tumours into two groups based on the expression of E2F-controlled genes was confirmed in a larger collection of anal carcinoma tumours. The expression of miR-15b was shown to be highly correlated with that of five selected E2F-induced genes (CCNA2, CCNB1, CCNB2, MSH6 and MCM7). A knockdown of HPV16 E7 resulted in decreased levels of miR-15b in Ca Ski cells.Conclusion:MiR-15b expression correlates with E2F-regulated genes in anal carcinoma and appears to be part of the E2F-regulatory network.
Highlights
MicroRNAs are important regulators of cellular processes and are found to be deregulated in many cancers
We demonstrated that tumours from patients with anal carcinomas could be divided into two distinct groups based on global mRNA expression (Bruland et al, 2008)
We searched for miRNAs that were differently expressed in anal tumours with higher vs lower expression of E2Finduced genes
Summary
MicroRNAs (miRNAs) are important regulators of cellular processes and are found to be deregulated in many cancers. We here analysed the miRNA expression in anal carcinomas. We found that our anal carcinoma tumours were divided into two groups based on the expression of E2F-regulated genes. Real-time – qPCR was used to verify the expression levels of selected miRNAs and genes in a larger collection of biopsies. RESULTS: The grouping of tumours into two groups based on the expression of E2F-controlled genes was confirmed in a larger collection of anal carcinoma tumours. A knockdown of HPV16 E7 resulted in decreased levels of miR-15b in Ca Ski cells. CONCLUSION: MiR-15b expression correlates with E2F-regulated genes in anal carcinoma and appears to be part of the E2F-regulatory network. British Journal of Cancer (2011) 105, 1719 – 1725. doi:10.1038/bjc.2011.457 www.bjcancer.com Published online 1 November 2011 & 2011 Cancer Research UK
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