Related Experiment Video
Updated: Jan 14, 2026
Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
Explicating miRNA-mediated regulation of inflammatory pathways in COPD, MS, and lung cancer using explainable
1Department of Biotechnology, Delhi Technological University Shahbad Daulatpur, Main Bawana Road, Delhi-110042, India.
Background:
Chronic obstructive pulmonary disease (COPD), multiple sclerosis (MS), and lung cancer are linked by shared inflammatory pathways and immune dysregulation. miRNAs regulate these processes by influencing gene expression, yet their roles in the molecular mechanisms across neurological and respiratory systems are not fully understood.
Objective:
This study aims to identify miRNAs and their target genes regulating inflammatory pathways, advancing the understanding of molecular genetics underlying COPD, MS, and lung cancer.
Methods:
miRNA expression data (GSE61741) were analyzed using a Random Forest (RF) model optimized via Grid Search and validated with Stratified K-Fold cross-validation. Synthetic Minority Oversampling (SMOTE) addressed data imbalance, while SHapley Additive exPlanations (SHAP) identified key miRNAs. Functional enrichment and pathway analyses explored miRNA-gene interactions. Single-cell level analysis further validated the cell-specific roles of these genes. An independent dataset (GSE31568) was used for validation.
Results:
Key miRNAs, including hsa-let-7c, hsa-miR-454, hsa-miR-92a, and hsa-miR-223, were identified as regulators of hallmark inflammatory genes such as CCL2, IL6, ITGB3, and MYC. These genes are critical for cytokine signaling, epithelial repair, and immune modulation. Single-cell analysis highlighted the role of inflammatory fibroblasts in localized inflammation and tissue remodeling. The RF model achieved an accuracy of 81.58%, validated at 82.55%. Pathway analysis emphasized cytokine-cytokine receptor interactions and shared pathways between neurological and respiratory diseases.
Conclusions:
This study identifies miRNAs and their target genes as critical regulators of inflammation in COPD, MS, and lung cancer. Single-cell insights and pathway enrichment provide a comprehensive view of shared molecular mechanisms, contributing to biomarker discovery and therapeutic strategies for precision medicine in inflammatory diseases.
Insights
This study identifies key microRNAs (miRNAs) and their target genes, like hsa-let-7c and CCL2, that regulate inflammation in chronic obstructive pulmonary disease (COPD), multiple sclerosis (MS), and lung cancer, paving the way for new precision medicine approaches.
Area of Science:
- Molecular biology
- Genetics
- Immunology
Background:
- Chronic obstructive pulmonary disease (COPD), multiple sclerosis (MS), and lung cancer share inflammatory pathways and immune dysregulation.
- MicroRNAs (miRNAs) are crucial regulators of gene expression, but their specific roles in these interconnected diseases are not fully understood.
Purpose of the Study:
- To identify specific miRNAs and their target genes involved in regulating inflammatory pathways common to COPD, MS, and lung cancer.
- To elucidate the molecular genetic underpinnings of these diseases for potential therapeutic advancements.
Main Methods:
- Analysis of miRNA expression data using a Random Forest model with Grid Search optimization and Stratified K-Fold cross-validation.
- Application of Synthetic Minority Oversampling (SMOTE) for data imbalance and SHapley Additive exPlanations (SHAP) for identifying key miRNAs.
- Functional enrichment, pathway analysis, and single-cell analysis to explore miRNA-gene interactions and cell-specific roles, validated on an independent dataset.
Main Results:
- Identification of key miRNAs (hsa-let-7c, hsa-miR-454, hsa-miR-92a, hsa-miR-223) regulating inflammatory genes (CCL2, IL6, ITGB3, MYC).
- These genes are critical for cytokine signaling, epithelial repair, and immune modulation, with inflammatory fibroblasts playing a role in tissue remodeling.
- The Random Forest model demonstrated high accuracy (81.58%–82.55%), and pathway analysis highlighted shared mechanisms between neurological and respiratory diseases.
Conclusions:
- MicroRNAs and their target genes are identified as critical regulators of inflammation in COPD, MS, and lung cancer.
- Single-cell insights and pathway analysis reveal shared molecular mechanisms, supporting biomarker discovery.
- Findings contribute to developing precision medicine strategies for inflammatory diseases.
Related Concept Videos
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation
01:20COPD: Pathogenesis and Clinical Features
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
01:17Drugs Used in Lower Respiratory Disorders: Overview
Bronchodilators, the first step of respiration enhancement, come in various forms, each with its own mechanism...