ABSTRACT
Endoplasmic reticulum stress (ERS) is a cellular defensive response to restore homeostasisand reduce the protein load. Over-activation of ERS can induce cell differentiation, proliferation, apoptosis, and autophagy. MicroRNAs (miRNAs) are endogenous non-coding RNAs (ncRNAs) thatregulate the expression of key proteins and genes in the ERS signaling pathway through post-transcriptional action. Meanwhile, activated ERS signaling pathway can indirectly regulate the expressionand function of target genes by decreasing miRNA stability. Based on a brief introduction of ERS classicalsignaling pathways, this paper further elaborated how microRNAs regulate ERS signaling pathways topromote apoptosis and proliferation, and what effect they would have on the expression profile of diseasesbased on this association. We also summarize the regulation of ERS on miRNAs expression and thecurrent research status. The mutual regulation between the two could provide a new idea for the follow-upresearch on the therapeutic targets of diseases.
ABSTRACT
The microRNA (miRNA) regulation mechanisms associated with atherosclerosis are largely undocumented. Specific selection and efficient validation of miRNA regulation pathways involved in atherosclerosis development may be better assessed by contemporary microarray platforms applying cross-verification methodology. A screening platform was established using both miRNA and genomic microarrays. Microarray analysis was then simultaneously performed on pooled atherosclerotic aortic tissues from 10 Apolipoprotein E (apoE) knockout mice (apoE-/-) and 10 healthy C57BL/6 (B6) mice. Differentiated miRNAs were screened and cross-verified against an mRNA screen database to explore integrative mRNA-miRNA regulation. Gene set enrichment analysis was conducted to describe the potential pathways regulated by these mRNA-miRNA interactions. High-throughput data analysis of miRNA and genomic microarrays of knockout and healthy control mice revealed 75 differentially expressed miRNAs in apoE-/- mice at a threshold value of 2. The six miRNAs with the greatest differentiation expression were confirmed by real-time quantitative reverse-transcription PCR (qRT-PCR) in atherosclerotic tissues. Significantly enriched pathways, such as the type 2 diabetes mellitus pathway, were observed by a gene-set enrichment analysis. The enriched molecular pathways were confirmed through qRT-PCR evaluation by observing the presence of suppressor of cytokine signaling 3 (SOCS3) and SOCS3-related miRNAs, miR-30a, miR-30e and miR-19b. Cross-verified high-throughput microarrays are optimally accurate and effective screening methods for miRNA regulation profiles associated with atherosclerosis. The identified SOCS3 pathway is a potentially valuable target for future development of targeted miRNA therapies to control atherosclerosis development and progression.