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Deciphering miR-520c-3p as a probable target for immunometabolism in non-small cell lung cancer using systems biology
Pooja Gulhane1, Prajakta Nimsarkar1, Komal Kharat1
1National Centre for Cell Science, NCCS Complex, Ganeshkhind, SP Pune University Campus, Pune 411007, India.
Background:
Non-small cell lung cancer (NSCLC) is considered to have more than 80% of all lung cancer cases, making it the leading cause of cancer-related deaths globally. MicroRNA (miRNA) deregulation has been seen often in NSCLC and has been linked to the disease's genesis, progression, and metastasis via affecting their target genes.
Materials And Methods:
Our study focused on the functionality of down-regulated miRNAs in NSCLC. For this study, we used 91 miRNAs reported to be down-regulated in NSCLC. The targets of these miRNAs were chosen from miRNA databases with functionality in NSCLC, including miRBase, miRDB, miRTV, and others. Inter-regulatory miRNA-NSCLC networks were generated. Simulated annealing was used to improve the network's resilience and understandability. GSEA was used to examine 24607 genes reported experimentally in order to gain physiologically relevant information about the target miR-520c-3p.
Results:
The study revealed functional prominence on miR-520c-3p, down-regulated during NSCLC. The involvement of miR-520c-3p in the PI3K/AKT/mTOR signaling pathway was recognized.
Conclusions:
The therapeutic usage by designing a synthetic circuit of miR-520c-3p was explored, which may help in suppressing tumors in NSCLC. Our study holds promise for the successful deployment of currently proposed miRNA-based therapies for malignant disorders, which are still in the early pre-clinical stages of development.
Insights
This study identifies miR-520c-3p as a key microRNA (miRNA) involved in non-small cell lung cancer (NSCLC). Therapeutic strategies targeting this miRNA show potential for future NSCLC treatments.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases globally.
- Dysregulation of microRNAs (miRNAs) is implicated in the development, progression, and metastasis of NSCLC.
Purpose of the Study:
- To investigate the functional roles of down-regulated miRNAs in NSCLC.
- To identify specific miRNAs and their target genes involved in NSCLC pathogenesis.
Main Methods:
- Analysis of 91 down-regulated miRNAs in NSCLC and their targets from multiple databases.
- Construction and optimization of inter-regulatory miRNA-NSCLC networks using simulated annealing.
- Gene Set Enrichment Analysis (GSEA) to understand the physiological relevance of target genes, focusing on miR-520c-3p.
Main Results:
- miR-520c-3p was identified as functionally significant and down-regulated in NSCLC.
- The involvement of miR-520c-3p in the PI3K/AKT/mTOR signaling pathway was established.
Conclusions:
- A synthetic circuit for miR-520c-3p was designed for potential therapeutic applications in NSCLC tumor suppression.
- This research supports the development of miRNA-based therapies for malignant diseases, currently in early pre-clinical stages.
