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Published on: March 30, 2019
Integrative analysis of candidate MicroRNAs and gene targets for OSA management using in silico and in-vitro approach
Gaganjyot Kaur Bakshi1, Sartaj Khurana1, Shambhavee Srivastav1
1Amity Institute of Biotechnology, Amity University Noida, Uttar Pradesh, India.
Abstract:
MicroRNAs (miRNAs) have been implicated in the pathogenesis of human diseases including sleep disorders. The aim of this study is to address the involvement of miRNAs (miR-21 and miR-29) in the pathophysiology of obstructive sleep apnea (OSA). In this study we have done integrated analysis of miRNAs with their potential gene targets as a strategy for management of OSA.
Methods:
miRNA expression levels were quantified in healthy control group and obese vs. Non-obese OSA subjects by Quantitative real-time PCR. In-silico analysis of interplay of miRNAs with potential gene targets was done using Schrödinger Release 2023-1.
Results:
The real time expression analysis revealed a differential expression pattern in miRNAs indicating down-regulation of miR-21 in obese OSA while miR-29 showed upregulation as compared to non-obese OSA and healthy subjects with p values of ≤0.01 and <0.0001respectively. A trend was observed where target genes TGFBR2, NAMPT, and NPPB were significantly increased with p-value of ≤0.0001 and TGFBR3 and INSIG2 showed decreasing trend with p-value of ≤0.0001 between obese and non-obese OSA respectively. MD simulation analysis provided valuable information regarding the stability, flexibility, compactness and solvent exposure of the complexes over time.
Conclusion:
miR-21 and miR-29 possesses differential expressions in obese OSA subject and exihbits strong molecular interactions with potential target genes, such as TGFBR2, NPPB, NAMPT and INSIG2. Identifying the miRNAs, genes and pathways associated with OSA can help to expand our understanding of the risk factors for the disease as well as provide new avenues for potential treatment.
Insights
MicroRNAs (miRNAs) miR-21 and miR-29 show altered expression in obstructive sleep apnea (OSA), particularly in obese individuals. These findings suggest potential diagnostic and therapeutic targets for OSA management.
Area of Science:
- Genetics
- Molecular Biology
- Sleep Medicine
Background:
- MicroRNAs (miRNAs) are implicated in human disease pathogenesis, including sleep disorders.
- Obstructive sleep apnea (OSA) is a prevalent condition with complex pathophysiology.
Purpose of the Study:
- To investigate the involvement of specific miRNAs (miR-21 and miR-29) in the pathophysiology of OSA.
- To analyze the integrated role of miRNAs and their gene targets as a management strategy for OSA.
Main Methods:
- Quantitative real-time PCR was used to measure miRNA expression levels in healthy controls and OSA subjects (obese vs. non-obese).
- In-silico analysis using Schrödinger Release 2023-1 was performed to predict miRNA-gene target interactions.
- Molecular dynamics (MD) simulations were conducted to assess the stability and interactions of miRNA-gene complexes.
Main Results:
- Differential expression of miR-21 (down-regulated in obese OSA) and miR-29 (up-regulated) was observed compared to non-obese OSA and healthy subjects.
- Significant alterations in target genes (TGFBR2, NAMPT, NPPB, TGFBR3, INSIG2) were identified in relation to OSA and obesity status.
- MD simulations provided insights into the dynamic behavior and stability of miRNA-target gene complexes.
Conclusions:
- miR-21 and miR-29 exhibit differential expression patterns in obese OSA patients and interact with key target genes (TGFBR2, NPPB, NAMPT, INSIG2).
- Identifying these miRNA-gene associations advances the understanding of OSA risk factors.
- These findings offer potential new avenues for OSA diagnosis and therapeutic interventions.
