Abstract
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.
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Availability of data and material
All data concerning the study were included into the manuscript and Supplementary Information.
Abbreviations
- DEGs:
-
Differentially expressed genes
- DEPs:
-
Differentially expressed proteins
- FPKM:
-
Fragments per kilo-base of exon per million fragments mapped
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- KO:
-
Knockout
- MiRNA:
-
MicroRNA
- TMT:
-
Tandem mass tag-based
- WT:
-
Wildtype
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Funding
This work was supported by grants from the national natural science foundation of China [81800882, 81870698, 82171109]; the national key R&D program of China [2018YFC0116800]; the program for the Changjiang scholars and innovative research team [IRT13082]; Beijing municipal administration of hospitals’ Mission/Dengfeng plan [SML20150203, DFL20190202]; CAMS Innovation Fund for Medical Sciences (2019-I2M-5-022); Beijing municipal science and technology project (Z181100001618002); and public welfare development and reform pilot project (2019–10).
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MW, CW and LZ designed the study. GL, MW, JY, XB and JS performed the experiments, analyzed the data and wrote the manuscript. C. and LZ critically revised the manuscript. All authors reviewed the manuscript.
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Luan, G., Wang, M., Yuan, J. et al. Regulatory network identified by pulmonary transcriptome and proteome profiling reveals extensive change of tumor-related genes in microRNA-21 knockout mice. J Cancer Res Clin Oncol 148, 1919–1929 (2022). https://doi.org/10.1007/s00432-022-03967-6
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DOI: https://doi.org/10.1007/s00432-022-03967-6