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Updated: Sep 24, 2025
Lung microRNA Profiling Across the Estrous Cycle in Ozone-exposed Mice
Published on: January 7, 2019
Regulatory network identified by pulmonary transcriptome and proteome profiling reveals extensive change of
Ge Luan1,2, Ming Wang1,2, Jing Yuan1,2
1Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, 100730, China.
Purpose:
MicroRNA-21 (miR-21) is a well-known oncomiR and plays key roles in regulating various biological processes related to pulmonary diseases, especially lung carcinoma. The regulatory roles and downstream targets of miR-21 remain far from well understood. We aimed to identify miR-21-gene regulatory network in lung tissue.
Methods:
Transcriptome and proteome analyses were performed on lung tissues from miR-21 knockout (KO) mice and their wildtype (WT) littermates. Differentially expressed genes (DEGs) and proteins (DEPs) between miR-21KO and WT were analyzed, and correlation analysis was performed between transcriptional and translational level. DEPs were used for prediction of miR-21 target genes and construction of co-expression network.
Results:
Comparing with WT mice, 820 DEGs and 623 DEPs were identified in lung tissues of miR-21KO mice. Upregulated DEGs and DEPs were both significantly enriched in pathways of metabolism of xenobiotics by cytochrome P450, drug metabolism, and chemical carcinogenesis. Of the 31 molecules commonly identified in DEGs and DEPs, 9 upregulated genes were tumor suppressor genes while 8 downregulated genes were oncogenes, and 12 genes showed closely positive correlation between mRNA and protein expression. Real-time PCR validation results were consistent with the omics data. Among the upregulated DEPs in miR-21KO mice, 21 genes were predicted as miR-21 targets. The miR-21 regulatory network was constructed by target genes and their highly co-expressed proteins, which identified the miR-21 target Itih4 as a hub gene.
Conclusion:
MiR-21-gene regulatory network was constructed in mouse lung tissue. MiR-21KO resulted in extensive upregulation of tumor suppressor genes and downregulation of oncogenes.
Insights
MicroRNA-21 (miR-21) knockout in mice lung tissue revealed a regulatory network impacting tumor suppressor and oncogenes. This study identified key miR-21 targets, advancing understanding of its role in lung disease.
Area of Science:
- Molecular Biology
- Genomics
- Proteomics
Background:
- MicroRNA-21 (miR-21) is an oncomiR implicated in pulmonary diseases, particularly lung carcinoma.
- The precise regulatory mechanisms and downstream targets of miR-21 in lung tissue are not fully elucidated.
Purpose of the Study:
- To identify the miR-21-gene regulatory network within mouse lung tissue.
- To understand the global impact of miR-21 on gene and protein expression in the lung.
Main Methods:
- Transcriptome and proteome analyses were conducted on lung tissues from miR-21 knockout (KO) and wildtype (WT) mice.
- Differential gene and protein expression analysis, correlation analysis between mRNA and protein levels, and prediction of miR-21 target genes were performed.
- A co-expression network was constructed using differentially expressed proteins to identify miR-21 regulatory interactions.
Main Results:
- 820 differentially expressed genes (DEGs) and 623 differentially expressed proteins (DEPs) were identified in miR-21 KO mice compared to WT mice.
- Upregulated DEGs and DEPs were enriched in pathways related to xenobiotic metabolism and chemical carcinogenesis.
- The study identified 9 upregulated tumor suppressor genes and 8 downregulated oncogenes among common DEGs and DEPs, and constructed a miR-21 regulatory network highlighting Itih4 as a hub gene.
Conclusions:
- A comprehensive miR-21-gene regulatory network was successfully constructed in mouse lung tissue.
- Deletion of miR-21 led to a significant upregulation of tumor suppressor genes and a downregulation of oncogenes in the lung.
- These findings provide critical insights into the role of miR-21 in lung carcinogenesis and suggest potential therapeutic targets.
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