MicroRNA‐mRNA network model in patients with achalasia. Issue 3 (26th November 2019)

• Record Type: Journal Article
• Authors: Palmieri, Orazio; Mazza, Tommaso; Bassotti, Gabrio; Merla, Antonio; Tolone, Salvatore; Biagini, Tommaso; Cuttitta, Antonello; Bossa, Fabrizio; Martino, Giuseppina; Latiano, Tiziana; Corritore, Giuseppe; Gioffreda, Domenica; Palumbo, Orazio; Carella, Massimo; Panza, Anna; Andriulli, Angelo; Latiano, Anna
• Is Part Of: Neurogastroenterology & motility. Volume 32:Issue 3(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-11-26
• Subjects: achalasia -- expression profile -- microRNA -- mRNA; Gastrointestinal system -- Motility -- Periodicals; Gastrointestinal system -- Innervation -- Periodicals; 616.33
• DOI: 10.1111/nmo.13764
• Languages: English
• ISSNs: 1350-1925

Abstract

Abstract: Background: Achalasia is a rare idiopathic disease with a complex etio‐pathogenesis still unknown. This study aimed to identify microRNA (miRNA)‐mRNA regulatory networks underlying achalasia. Methods: The investigation was performed in tissue specimens from 11 patients and five controls using the microarray technology followed by an integrated bioinformatics analysis. Key Results: One hundred and six miRNAs were significantly up‐regulated and 64 were down‐regulated in achalasia patients. The expression of the most 10 differential expressed miRNAs (miR‐122‐5p, miR‐133a‐3p, miR‐504‐5p, miR‐187‐3p, miR‐133b, miR‐200c‐3p, miR‐375, miR‐200b‐5p, miR‐200b‐3p, and miR203a) was confirmed by droplet digital PCR in an independent cohort. The interactions between the significant miRNAs and their targets uncovered 14 miRNA‐mRNA interacting pairs with experimentally predicted genes (ie, FN1, ROCK2, DPYSL2 ), and 35 pairs with not experimentally target genes (ie, SULF1, MRVI1, PRKG1 ); all genes were involved in immune cell trafficking, skeletal and muscular system development, nervous system development macro‐processes. Conclusion & Inferences: The mRNA–miRNA regulatory networks described in this study provide new insights in the genetic background of the disease, suggesting further investigations in novel pathogenic mechanisms. Abstract : By using microarray technology we identify miRNAs with differential expression in muscle specimens of achalasic compared with non‐achalasic subjects. The integrative analysis of miRNA‐mRNA expression data has highlighted that differentially expressed miRNAs regulate genes involved in contraction of smooth muscle and synaptic transmission of cells signaling pathways, playing an important role in the relaxation of smooth muscle cells and in neuronal cell death.