In silico analysis of pathways affected by differentially expressed microRNAs in adrenocortical tumors

Zsippai, A. and Szabó, P. M. and Szabó, D. R. and Nagy, Z. and Patócs, A. B. and Rácz, K. and Igaz, P. (2013) In silico analysis of pathways affected by differentially expressed microRNAs in adrenocortical tumors. JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 36 (11). pp. 1011-1019. ISSN 0391-4097

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Abstract

Background: MicroRNAs are involved in the pathogenesis of several tumors, and several studies have been performed on the microRNA profile of adrenocortical tumors to date. The pathways affected by these microRNAs, however, have not been analyzed yet by a systematic approach. Aim: To perform an in silico bioinformatics analysis of microRNAs commonly altered in at least two studies and to decipher the pathways affected by microRNAs in adrenocortical tumors. Methods: Datasets on microRNA and mRNA expression have been retrieved from five and three studies, respectively. MicroRNA mRNA targets have been identified by our tissue specific target prediction pipeline, and mRNAs have been subjected to Ingenuity Pathway Analysis. Results: 39 microRNAs were identified as commonly altered in two studies. Altogether 49817 mRNA targets have been found for these microRNAs. 178 significant pathways associating with these have been identified that were found in all studies. We have selected 12 pathways involving retinoic acid signaling (LPS/IL-1 mediated inhibition of RXR function, PPARalpha/RXRalpha activation, RAR activation and PPAR signaling pathways) and cell cycle alterations (aryl hydrocarbon receptor signaling, GADD45 signaling, integrin signaling, G2/M DNA damage checkpoint regulation, cyclins and cell cycle regulation and cell cycle control of chromosomal replication pathways) as these have been also established in our previous study on the functional genomics meta-analysis of adrenocortical tumors. Several microRNAs have been identified that could affect these pathways. Conclusions: MicroRNAs might affect several pathogenic pathways in adrenocortical tumors. Validation studies are required to confirm the biological relevance of these findings.

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