Integrated microRNA and protein expression analysis reveals novel microRNA regulation of targets in fetal down syndrome

Abstract

Down syndrome (DS) is caused by trisomy of human chromosome 21 and is associated with a number of deleterious phenotypes. To investigate the role of microRNA (miRNA) in the regulation of DS, high-throughput Illumina sequencing technology and isobaric tagging for relative and absolute protein quantification analysis were utilized for simultaneous expression profiling of miRNA and protein in fetuses with DS and normal fetuses. A total of 344 miRNAs were associated with DS. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to investigate the proteins found to be differentially expressed. Functionally important miRNAs were determined by identifying enriched or depleted targets in the transcript and the protein expression levels were consistent with miRNA regulation. The results indicated that GRB2, TMSB10, RUVBL2, the hsa-miR-329 and hsa-miR-27b, hsa-miR-27a targets, and MAPK1, PTPN11, ACTA2 and PTK2 or other differentially expressed proteins were connected with each other directly or indirectly. Integrative analysis of miRNAs and proteins provided an expansive view of the molecular signaling pathways in DS.

Differential microRNA expression profile in blood of children with Down syndrome suggests a role in immunological dysfunction

“…The six DEmiRs identified in the present study between children with DS and controls are not located on HSA21; four of them were observed to be upregulated (miR-378a-3p, miR-130b-5p, miR-942-5p, and miR-424-3p) and two downregulated (miR-452-5p and miR-668-3p). Although some DEmiRs identified in the present study have been previously found to be dysregulated in other DS tissues [35][36][37], to our knowledge, this is the first study to report altered expression of these six DEmiRs in PBMCs from individuals with DS. Altered expression of miRNAs not located on HSA21 with possible involvement in DS phenotypes has been previously reported [33][34][35][36][37][38][39][40], supporting the existing hypothesis of secondary transcriptional changes as a consequence of the trisomy 21 [41].…”

“…Although some DEmiRs identified in the present study have been previously found to be dysregulated in other DS tissues [35][36][37], to our knowledge, this is the first study to report altered expression of these six DEmiRs in PBMCs from individuals with DS. Altered expression of miRNAs not located on HSA21 with possible involvement in DS phenotypes has been previously reported [33][34][35][36][37][38][39][40], supporting the existing hypothesis of secondary transcriptional changes as a consequence of the trisomy 21 [41].…”

Mature miR-99a Upregulation in the Amniotic Fluid Samples from Female Fetus Down Syndrome Pregnancies: A Pilot Study

“…The first three belong to a cluster located within the C21orf34, miR-802 is located inside RUNX1, while miR-155 is located within MIR155HG (MIR155 host gene) as part of BIC (B cell integration) cluster. Bioinformatics analyses of miR(21) predict over 2000 putative targets, which suggest that if deregulated, miR(21) might play an important role in DS pathogenesis [17].…”