hsa-miR-106b-5p participates in the development of chronic thromboembolic pulmonary hypertension via targeting matrix metalloproteinase 2

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by elevated pressure in pulmonary arteries. This study was performed to explore the critical miRNAs and genes affecting the pathogenesis of CTEPH.

Methods: GSE56914 dataset (10 CTEPH whole blood samples and 10 control samples) was downloaded from the Gene Expression Omnibus database. Using limma package, the differentially expressed miRNAs (DE-miRNAs) were acquired. After miRNA-target pairs were obtained using miRWalk2.0 tool, a miRNA-target regulatory network was built by Cytoscape software. Using DAVID tool, significantly enriched pathways involving the target genes were identified. Moreover, the protein-protein interaction network and transcription factor-target regulatory network were built by the Cytoscape software. Additionally, quantitative real-time PCR (qRT-PCR) experiments and luciferase assay were conducted to validate miRNA/gene expression and miRNA-target regulatory relationship, respectively.

Results: There were 25 DE-miRNAs (8 up-regulated and 17 down-regulated) between CTEPH and control groups. The target genes of has-let-7b-3p, has-miR-17-5p, has-miR-3202, has-miR-106b-5p, and has-miR-665 were enriched in multiple pathways such as "Insulin secretion". qRT-PCR analysis confirmed upregulation of hsa-miR-3202, hsa-miR-665, and matrix metalloproteinase 2 (MMP2) as well as downregulation of hsa-let-7b-3p, hsa-miR-17-5p, and hsa-miR-106b-5p. Luciferase assay indicated that MMP2 was negatively mediated by hsa-miR-106b-5p.

Conclusions: These miRNAs and genes were associated with the pathogenesis of CTEPH. Besides, hsa-miR-106b-5p was involved in the development of CTEPH via targeting MMP2.