Molekularbiologie: Open Access

hsa-miR-149-5p Diminish MAPK and PI3K/Akt Signalling Pathways through Down-regulation of ERbB3 in SLE Patients

Abstract

Ghods FJ, Sarikaya AT, Arda N and Hamuryudan V

Introduction: In Systemic Lupus, miRNAs construct a substantial layer of post-transcriptional gene expression regulation. Availability of sensitive and specific methods for their detection makes them candidates for potential biomarker discovery. Here we compared miRNAs particular to SLE patients with healthy controls.
Methods: Total RNA and miRNAs were isolated from blood and serum of 16 SLE patients and 8 healthy controls for microarray assays. Potential target genes were predicted and interrogated with mRNA profiling data. BLAST alignment analysis was done between differentially expressed miRNAs and predicted target genes. Microarray results were confirmed by QRT-PCR.
Results: 10 miRNAs were differently expressed in SLE patients of which, has-miR-149-5p was up-regulated about 8.5 fold. Among predicted targets only ERbB3 approved by mRNA profiling and found to be down-regulated approximately by two fold. BLAST alignment analysis of mature sequence of has-miR-149-5p and ERbB3 sequence revealed that 16 of 18 nucleotides belong to hsa-miR-149-5p, matched with nucleotides in minus chain of target gene (89%). Two nucleotides “mismatches” did not interfere with target mRNA degradation.
Conclusion: We conclude hsa-miR-149-5p degrades ERbB3 gene’s primary transcript before splicing meaning that up-regulation of hsa-miR-149-5p activates direct/indirect apoptosis by stopping ERbB3 translation and could be a biomarker candidate for lupus activity.