Abstract
IntroductionMicroRNAs are regulators of central cellular processes and are implicated in the pathogenesis and prognosis of human cancers. MicroRNAs also modulate responses to anti-cancer therapy. In the context of radiation oncology microRNAs were found to modulate cell death and proliferation after irradiation. However, changes in microRNA expression profiles in response to irradiation have not been comprehensively analyzed so far. The present study's intend is to present a broad screen of changes in microRNA expression following irradiation of different malignant cell lines.Materials and methods1100 microRNAs (Sanger miRBase release version 14.0) were analyzed in six malignant cell lines following irradiation with clinically relevant doses of 2.0 Gy. MicroRNA levels 6 hours after irradiation were compared to microRNA levels in non-irradiated cells using the "Geniom Biochip MPEA homo sapiens".ResultsHierarchical clustering analysis revealed a pattern, which significantly (p = 0.014) discerned irradiated from non-irradiated cells. The expression levels of a number of microRNAs known to be involved in the regulation of cellular processes like apoptosis, proliferation, invasion, local immune response and radioresistance (e. g. miR-1285, miR-24-1, miR-151-5p, let-7i) displayed 2 - 3-fold changes after irradiation. Moreover, several microRNAs previously not known to be radiation-responsive were discovered.ConclusionIonizing radiation induced significant changes in microRNA expression profiles in 3 glioma and 3 squamous cell carcinoma cell lines. The functional relevance of these changes is not addressed but should by analyzed by future work especially focusing on clinically relevant endpoints like radiation induced cell death, proliferation, migration and metastasis.
Highlights
MicroRNAs are regulators of central cellular processes and are implicated in the pathogenesis and prognosis of human cancers
The expression levels of a number of microRNAs known to be involved in the regulation of cellular processes like apoptosis, proliferation, invasion, local immune response and radioresistance (e. g. miR-1285, miR-24-1, miR-151-5p, let-7i) displayed 2 - 3-fold changes after irradiation
The functional relevance of these changes is not addressed but should by analyzed by future work especially focusing on clinically relevant endpoints like radiation induced cell death, proliferation, migration and metastasis
Summary
MicroRNAs are regulators of central cellular processes and are implicated in the pathogenesis and prognosis of human cancers. In the context of radiation oncology microRNAs were found to modulate cell death and proliferation after irradiation. MicroRNAs are small non-coding RNAs of typically 20 22 base pairs length. They are involved in gene regulation at the post-transcriptional level by silencing mRNA translation. MicroRNAs are involved in the regulation of diverse cellular processes, including programmed cell death, proliferation, differentiation, metabolism, migration and stress responses (for review see [1]). As central regulators of gene expression, microRNAs have been implicated in the pathogenesis of human cancers, acting either as tumor suppressors [3,4] or as oncogenes [5]. Normal cells show altered levels of microRNAs in response to ionizing radiation [12,13]
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