{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pei J"],"funding":["the Natural Science Foundation of Gansu Province","the Lanzhou Science and Technology Bureau"],"pagination":["250"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10916124"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(1)"],"pubmed_abstract":["<h4>Background</h4>Immunotherapy is a practical therapeutic approach in breast cancer (BRCA), and the role of FLI1 in immune regulation has gradually been unveiled. However, the specific role of FLI1 in BRCA was conflicted; thus, additional convincing evidence is needed.<h4>Methods</h4>We explored the upstream regulation of FLI1 expression via summary data-based Mendelian randomization (SMR) analysis and ncRNA network construction centering on FLI1 using BRCA genome-wide association study (GWAS) summary data with expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci (mQTLs) from the blood and a series of in silico analyses, respectively. We illuminated the downstream function of FLI1 in immune regulation by integrating a series of analyses of single-cell RNA sequence data (scRNA-seq).<h4>Results</h4>We verified a causal pathway from FLI1 methylation to FLI1 gene expression to BRCA onset and demonstrated that FLI1 was downregulated in BRCA. FLI1, a transcription factor, served as myeloid and T cells' communication regulator by targeting immune-related ligands and receptor transcription in BRCA tissues. We constructed a ceRNA network centering on FLI1 that consisted of three LncRNAs (CKMT2-AS1, PSMA3-AS1, and DIO3OS) and a miRNA (hsa-miR-324-5p), and the expression of FLI1 was positively related to a series of immune-related markers, including immune cell infiltration, biomarkers of immune cells, and immune checkpoints.<h4>Conclusion</h4>Low-methylation-induced or ncRNA-mediated downregulation of FLI1 is associated with poor prognosis, and FLI1 might regulate the tumor immune microenvironment via a cell-type-specific target genes manner in BRCA."],"journal":["BMC genomics"],"pubmed_title":["Integrated analysis reveals FLI1 regulates the tumor immune microenvironment via its cell-type-specific expression and transcriptional regulation of distinct target genes of immune cells in breast cancer."],"pmcid":["PMC10916124"],"funding_grant_id":["22JR5RA191","23JRRA1381","2022-ZD-62"],"pubmed_authors":["Lan C","Peng Y","Li Y","Zhang T","Pei J","Ma K","Chen X","Gao H"],"additional_accession":[]},"is_claimable":false,"name":"Integrated analysis reveals FLI1 regulates the tumor immune microenvironment via its cell-type-specific expression and transcriptional regulation of distinct target genes of immune cells in breast cancer.","description":"<h4>Background</h4>Immunotherapy is a practical therapeutic approach in breast cancer (BRCA), and the role of FLI1 in immune regulation has gradually been unveiled. However, the specific role of FLI1 in BRCA was conflicted; thus, additional convincing evidence is needed.<h4>Methods</h4>We explored the upstream regulation of FLI1 expression via summary data-based Mendelian randomization (SMR) analysis and ncRNA network construction centering on FLI1 using BRCA genome-wide association study (GWAS) summary data with expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci (mQTLs) from the blood and a series of in silico analyses, respectively. We illuminated the downstream function of FLI1 in immune regulation by integrating a series of analyses of single-cell RNA sequence data (scRNA-seq).<h4>Results</h4>We verified a causal pathway from FLI1 methylation to FLI1 gene expression to BRCA onset and demonstrated that FLI1 was downregulated in BRCA. FLI1, a transcription factor, served as myeloid and T cells' communication regulator by targeting immune-related ligands and receptor transcription in BRCA tissues. We constructed a ceRNA network centering on FLI1 that consisted of three LncRNAs (CKMT2-AS1, PSMA3-AS1, and DIO3OS) and a miRNA (hsa-miR-324-5p), and the expression of FLI1 was positively related to a series of immune-related markers, including immune cell infiltration, biomarkers of immune cells, and immune checkpoints.<h4>Conclusion</h4>Low-methylation-induced or ncRNA-mediated downregulation of FLI1 is associated with poor prognosis, and FLI1 might regulate the tumor immune microenvironment via a cell-type-specific target genes manner in BRCA.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-23T03:10:38.064Z","creation":"2026-06-23T03:09:14.881Z"},"accession":"S-EPMC10916124","cross_references":{"pubmed":["38448802"],"doi":["10.1186/s12864-024-10174-9"]}}