In silico analysis to identify miR-1271-5p/PLCB4 (phospholipase C Beta 4) axis mediated oxaliplatin resistance in metastatic colorectal cancer.

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Although there have been numerous studies on OXA resistance, but its underlying molecular mechanisms are still unclear. This study aims to identify key regulatory genes and pathways associated with OXA resistance. The Gene Expression Omnibus (GEO) GSE42387 dataset containing gene expression profiles of parental and OXA-resistant LoVo cells was applied to explore potential targets. GEO2R, STRING, CytoNCA (a plug-in of Cytoscape), and DAVID were used to analyze differentially expressed genes (DEGs), protein-protein interactions (PPIs), hub genes in PPIs, and gene ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. R2 online platform was used to run a survival analysis of validated hub genes enriched in KEGG pathways. The ENCORI database predicted microRNAs for candidate genes. A survival analysis of those genes was performed, and validated using the OncoLnc database. In addition, the 'clusterProfiler' package in R was used to perform gene set enrichment analysis (GSEA). We identified 395 DEGs, among which 155 were upregulated and 240 were downregulated. In total, 95 DEGs were screened as hub genes after constructing the PPI networks. Twelve GO terms and three KEGG pathways (steroid hormone biosynthesis, malaria, and pathways in cancer) were identified as being significant in the enrichment analysis of hub genes. Twenty-one hub genes enriched in KEGG pathways were defined as key genes. Among them AKT3, phospholipase C Beta 4 (PLCB4), and TGFB1 were identified as OXA-resistance genes through the survival analysis. High expressions of AKT3 and TGFB1 were each associated with a poor prognosis, and lower expression of PLCB4 was correlated with worse survival. Further, high levels of hsa-miR-1271-5p, which potentially targets PLCB4, were associated with poor overall survival in patients with CRC. Finally, we found that PLCB4 low expression was associated with MAPK signaling pathway and VEGF signaling pathway in CRC. Our results demonstrated that hsa-miR-1271-5p/PLCB4 in the pathway in cancer could be a new potential therapeutic target for mCRC with OXA resistance.", "claims": [{"id": "claim-data-access", "statement": "The dataset supporting the conclusions of this article is included within the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36927770", "locator": "sections[28] \"notes\" paragraph 1", "quote": "The dataset supporting the conclusions of this article is included within the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In total, 395 DEGs were predicted to be related to OXA resistance after calculation of log (FC) and p values; among these, 155 DEGs were upregulated and 240 DEGs were downregulated (Fig. 2A, Supplemental Fig. 1, Supplemental Table 1).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36927770", "locator": "sections[12] \"Identification of DEGs and heat map clustering analysis\" paragraph 2", "quote": "In total, 395 DEGs were predicted to be related to OXA resistance after calculation of log (FC) and p values; among these, 155 DEGs were upregulated and 240 DEGs were downregulated (Fig. 2A, Supplemental Fig. 1, Supplemental Table 1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In total, 395 DEGs were predicted to be related to OXA resistance after calculation of log (FC) and p values; among these, 155 DEGs were upregulated and 240 DEGs were downregulated (Fig. 2A, Supplemental Fig. 1, Supplemental Table 1).", "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:36927770"], "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. 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