Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies
Abstract Background Colorectal cancer (CRC) is a prevalent malignancy worldwide, with increasing incidence and mortality rates. Although treatment options have improved, CRC remains a leading cause of death due to metastasis. Early intervention can significantly improve patient outcomes, making it c...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12920-023-01763-w |
| _version_ | 1797388027409989632 |
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| author | Huimin Liu Xingxing Wu Dandan Wang Quanxi Li Xin Zhang Liang Xu |
| author_facet | Huimin Liu Xingxing Wu Dandan Wang Quanxi Li Xin Zhang Liang Xu |
| author_sort | Huimin Liu |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer (CRC) is a prevalent malignancy worldwide, with increasing incidence and mortality rates. Although treatment options have improved, CRC remains a leading cause of death due to metastasis. Early intervention can significantly improve patient outcomes, making it crucial to understand the molecular mechanisms underlying CRC metastasis. In this study, we performed bioinformatics analysis to identify potential genes associated with CRC metastasis. Methods We downloaded and integrated gene expression datasets (GSE89393, GSE100243, and GSE144259) from GEO database. Differential expression analysis was conducted, followed by Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub gene SERPINA3 was selected for further in vitro functional studies. Additionally, the role of miR-137-3p/miR-296-5p/ Serpin family A member 3 (SERPINA3) in CRC cell function was investigated using in vitro assays. Results Analysis of the gene expression datasets revealed differentially expressed genes (DEGs) associated with CRC metastasis. GO analysis showed enrichment in biological processes such as blood coagulation regulation and wound healing. Cellular component analysis highlighted extracellular matrix components and secretory granules. Molecular function analysis identified activities such as serine-type endopeptidase inhibition and lipoprotein receptor binding. KEGG analysis revealed involvement in pathways related to complement and coagulation cascades, cholesterol metabolism, and immune responses. The common DEGs among the datasets were further investigated. We identified SERPINA3 as a hub gene associated with CRC metastasis. SERPINA3 exerted enhanced effects on migration, proliferation and epithelial-mesenchymal transition (EMT) and inhibitory effects on caspase-3/-9 activities in HT29 and SW620 cells. MiR-137-3p overexpression increased activities of caspase-3/-9, decreased migration and proliferation, and also repressed EMT in HT29 cells, which were obviously attenuated by SERPINA3 enforced overexpression. Consistently, SERPINA3 enforced overexpression also largely reversed miR-296-5p mimics-induced increased in activities of caspase-3/-9, decrease in migration, proliferation and EMT in HT29 cells. Conclusion Through bioinformatics analysis, we identified potential genes associated with CRC metastasis. The functional studies focusing on SERPINA3/miR-137-3p/miR-296-5p further consolidated its role in regulating CRC progression. Our findings provide insights into novel mechanisms underlying CRC metastasis and might contribute to the development of effective treatment strategies. However, the role of SERPINA3/miR-137-3p/miR-296-5p signaling in CRC still requires further investigation. |
| first_indexed | 2024-03-08T22:34:45Z |
| format | Article |
| id | doaj.art-de229f21ed254e8fa66007a82bd27103 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-03-08T22:34:45Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-de229f21ed254e8fa66007a82bd271032023-12-17T12:32:50ZengBMCBMC Medical Genomics1755-87942023-12-0116111610.1186/s12920-023-01763-wUnveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studiesHuimin Liu0Xingxing Wu1Dandan Wang2Quanxi Li3Xin Zhang4Liang Xu5Department of General Surgery, The Second People’s Hospital of LianyungangDepartment of Pediatric Surgery, The Second People’s Hospital of LianyungangDepartment of General Surgery, The Second People’s Hospital of LianyungangDepartment of General Surgery, The Second People’s Hospital of LianyungangDepartment of General Surgery, The Second People’s Hospital of LianyungangDepartment of General Surgery, The Second People’s Hospital of LianyungangAbstract Background Colorectal cancer (CRC) is a prevalent malignancy worldwide, with increasing incidence and mortality rates. Although treatment options have improved, CRC remains a leading cause of death due to metastasis. Early intervention can significantly improve patient outcomes, making it crucial to understand the molecular mechanisms underlying CRC metastasis. In this study, we performed bioinformatics analysis to identify potential genes associated with CRC metastasis. Methods We downloaded and integrated gene expression datasets (GSE89393, GSE100243, and GSE144259) from GEO database. Differential expression analysis was conducted, followed by Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub gene SERPINA3 was selected for further in vitro functional studies. Additionally, the role of miR-137-3p/miR-296-5p/ Serpin family A member 3 (SERPINA3) in CRC cell function was investigated using in vitro assays. Results Analysis of the gene expression datasets revealed differentially expressed genes (DEGs) associated with CRC metastasis. GO analysis showed enrichment in biological processes such as blood coagulation regulation and wound healing. Cellular component analysis highlighted extracellular matrix components and secretory granules. Molecular function analysis identified activities such as serine-type endopeptidase inhibition and lipoprotein receptor binding. KEGG analysis revealed involvement in pathways related to complement and coagulation cascades, cholesterol metabolism, and immune responses. The common DEGs among the datasets were further investigated. We identified SERPINA3 as a hub gene associated with CRC metastasis. SERPINA3 exerted enhanced effects on migration, proliferation and epithelial-mesenchymal transition (EMT) and inhibitory effects on caspase-3/-9 activities in HT29 and SW620 cells. MiR-137-3p overexpression increased activities of caspase-3/-9, decreased migration and proliferation, and also repressed EMT in HT29 cells, which were obviously attenuated by SERPINA3 enforced overexpression. Consistently, SERPINA3 enforced overexpression also largely reversed miR-296-5p mimics-induced increased in activities of caspase-3/-9, decrease in migration, proliferation and EMT in HT29 cells. Conclusion Through bioinformatics analysis, we identified potential genes associated with CRC metastasis. The functional studies focusing on SERPINA3/miR-137-3p/miR-296-5p further consolidated its role in regulating CRC progression. Our findings provide insights into novel mechanisms underlying CRC metastasis and might contribute to the development of effective treatment strategies. However, the role of SERPINA3/miR-137-3p/miR-296-5p signaling in CRC still requires further investigation.https://doi.org/10.1186/s12920-023-01763-wColorectal cancerMetastasisBioinformatics analysisDEGsSERPINA3, miR-137-3pmiR-296-5p |
| spellingShingle | Huimin Liu Xingxing Wu Dandan Wang Quanxi Li Xin Zhang Liang Xu Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies BMC Medical Genomics Colorectal cancer Metastasis Bioinformatics analysis DEGs SERPINA3, miR-137-3p miR-296-5p |
| title | Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies |
| title_full | Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies |
| title_fullStr | Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies |
| title_full_unstemmed | Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies |
| title_short | Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies |
| title_sort | unveiling the role of mir 137 3p mir 296 5p serpina3 signaling in colorectal cancer progression integrative analysis of gene expression profiles and in vitro studies |
| topic | Colorectal cancer Metastasis Bioinformatics analysis DEGs SERPINA3, miR-137-3p miR-296-5p |
| url | https://doi.org/10.1186/s12920-023-01763-w |
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