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

Background: MicroRNA 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 microRNA, however, have not been analyzed yet by a systematic approach.

Aim: To perform an in silico bioinformatics analysis of microRNA commonly altered in at least two studies and to decipher the pathways affected by microRNA in adrenocortical tumors.

Methods: Datasets on microRNA and mRNA expression have been retrieved from 5 and 3 studies, respectively. MicroRNA mRNA targets have been identified by our tissue specific target prediction pipeline, and mRNA have been subjected to Ingenuity Pathway Analysis.

Results: Thirty- nine microRNA were identified as commonly altered in two studies. Altogether 49,817 mRNA targets have been found for these microRNA. One-hundred and seventy-eight significant pathways associating with these have been identified and were found in all studies. We have selected 12 pathways involving retinoic acid signaling (lipopolysaccharide/ interleukin-1 mediated inhibition of retinoic X receptor (RXR) function, peroxisome proliferator-activated receptor (PPAR)α/RXRα activation, retinoic A receptor activation and PPAR signaling pathways) and cell cycle alterations (aryl hydrocarbon receptor signaling, growth arrest and DNA damage-inducible 45 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 microRNA have been identified that could affect these pathways.

Conclusions: MicroRNA might affect several pathogenic pathways in adrenocortical tumors. Validation studies are required to confirm the biological relevance of these findings.