Identification of Hedyotis diffusa Willd-specific mRNA–miRNA–lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification
Abstract Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-56880-y |
| _version_ | 1797259330900197376 |
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| author | Jing Jiang Meng Huang Si-Si Zhang Yong-Gang Wu Xiao-Long Li Hui Deng Xin-Yu Qili Jian-Lin Chen Yao Meng Wen-Kui Sun |
| author_facet | Jing Jiang Meng Huang Si-Si Zhang Yong-Gang Wu Xiao-Long Li Hui Deng Xin-Yu Qili Jian-Lin Chen Yao Meng Wen-Kui Sun |
| author_sort | Jing Jiang |
| collection | DOAJ |
| description | Abstract Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA–miRNA–lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW’s regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA’s progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA. |
| first_indexed | 2024-04-24T23:07:43Z |
| format | Article |
| id | doaj.art-1722510437d5412b9073fdae0d617a57 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T23:07:43Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1722510437d5412b9073fdae0d617a572024-03-17T12:22:50ZengNature PortfolioScientific Reports2045-23222024-03-0114111610.1038/s41598-024-56880-yIdentification of Hedyotis diffusa Willd-specific mRNA–miRNA–lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verificationJing Jiang0Meng Huang1Si-Si Zhang2Yong-Gang Wu3Xiao-Long Li4Hui Deng5Xin-Yu Qili6Jian-Lin Chen7Yao Meng8Wen-Kui Sun9School of Laboratory Medicine, Chengdu Medical CollegeSchool of Laboratory Medicine, Chengdu Medical CollegeSchool of Laboratory Medicine, Chengdu Medical CollegeDepartment of Orthopedics, Xindu District People’s HospitalDepartment of Orthopedics, Xindu District Hospital of Traditional Chinese MedicineDepartment of Clinical Laboratory, Sichuan Taikang HospitalSchool of Laboratory Medicine, Chengdu Medical CollegeSchool of Laboratory Medicine, Chengdu Medical CollegeSchool of Laboratory Medicine, Chengdu Medical CollegeSchool of Laboratory Medicine, Chengdu Medical CollegeAbstract Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA–miRNA–lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW’s regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA’s progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA.https://doi.org/10.1038/s41598-024-56880-y |
| spellingShingle | Jing Jiang Meng Huang Si-Si Zhang Yong-Gang Wu Xiao-Long Li Hui Deng Xin-Yu Qili Jian-Lin Chen Yao Meng Wen-Kui Sun Identification of Hedyotis diffusa Willd-specific mRNA–miRNA–lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification Scientific Reports |
| title | Identification of Hedyotis diffusa Willd-specific mRNA–miRNA–lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification |
| title_full | Identification of Hedyotis diffusa Willd-specific mRNA–miRNA–lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification |
| title_fullStr | Identification of Hedyotis diffusa Willd-specific mRNA–miRNA–lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification |
| title_full_unstemmed | Identification of Hedyotis diffusa Willd-specific mRNA–miRNA–lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification |
| title_short | Identification of Hedyotis diffusa Willd-specific mRNA–miRNA–lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification |
| title_sort | identification of hedyotis diffusa willd specific mrna mirna lncrna network in rheumatoid arthritis based on network pharmacology bioinformatics analysis and experimental verification |
| url | https://doi.org/10.1038/s41598-024-56880-y |
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