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pmid:38087342
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.
Huimin Liu · Xingxing Wu · Dandan Wang · Quanxi Li · Xin Zhang · Liang Xu
BMC medical genomics · 2023 doi:10.1186/s12920-023-01763-w
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Complete file
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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.\nMETHODS: 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.\nRESULTS: 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.\nCONCLUSION: 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.", "claims": [{"id": "claim-method", "statement": "For comparisons, appropriate statistical tests including the Student’s t-test and one-way analysis of variance followed by Bonferroni’s post-hoc tests were performed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38087342", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "For comparisons, appropriate statistical tests including the Student’s t-test and one-way analysis of variance followed by Bonferroni’s post-hoc tests were performed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the data are available upon reasonable request from corresponding author. 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GSE89393 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89393_, GSE100243 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100243) and GSE144259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE144259)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "SERPINA3 was identified as a hub gene associated with CRC metastasis, and the functional studies further established a role for SERPINA3/miR-137-3p/miR-296-5p in regulating CRC progression.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38087342", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified SERPINA3 as a hub gene associated with CRC metastasis."}, {"asset": "source:pmid:38087342", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The functional studies focusing on SERPINA3/miR-137-3p/miR-296-5p further consolidated its role in regulating CRC progression."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "SERPINA3 was identified as a hub gene associated with CRC metastasis, and the functional studies further established a role for SERPINA3/miR-137-3p/miR-296-5p in regulating CRC progression.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38087342"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE100243"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE100243"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38087342", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12920-023-01763-w", "sha256": "sha256:6217781aa6a99b9ad1dd0d5b4b1057cc0ee071cdd8e75febd294b5b70eec7310", "bytes": 51055, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12920-023-01763-w", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10714458", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE100243", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100243", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE100243", "version": null, "note": "All the data are available upon reasonable request from corresponding author. 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