Identification of exosomal miR-455-5p and miR-1255a as therapeutic targets for breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31763681", "kind": "science-record", "revision": 9, "content_hash": "sha256:452700bf4cf1b015bbe2f3a759499b96c0b1d20f7f80b117eaf3fe541234e13e", "created_at": "2026-11-01T15:40:52Z", "updated_at": "2026-11-01T22:44:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of exosomal miR-455-5p and miR-1255a as therapeutic targets for breast cancer.", "doi": "10.1042/BSR20190303", "pmid": "31763681", "authors": ["Ying Xin", "Xueqiang Wang", "Kexin Meng", "Chao Ni", "Zhenye Lv", "Dandan Guan"], "journal": "Bioscience reports", "year": 2020, "abstract": "Accumulated evidence has demonstrated exosomes of cancer cells carry microRNAs (miRNAs) to non-malignant cells to induce metastasis. The present study aimed to identify crucial exosomal miRNAs for breast cancer (BC) using microarray data (GSE83669 and GSE50429) from Gene Expression Omnibus database, including exosomal samples from human BC cells (MCF7, MDA-MB-231) and normal mammary epithelial cell line (MCF10, MCF-10A), as well as original cell samples. Differentially expressed miRNAs (DEMs) were identified using EdgeR package, and mRNA targets were predicted using miRWalk2 database. The target genes were overlapped with BC genes from Comparative Toxicogenomics Database (CTD) to construct BC-related interaction network. Potential functions were analyzed by DAVID. The expression of crucial miRNAs and target genes were confirmed in other microarray datasets or TCGA sequencing data. Their associations with survival and other clinical characteristics were validated by Kaplan-Meier plotter and LinkedOmics database. As a result, 9 and 8 DEMs were identified to be shared in two datasets for exosomal and original cells, respectively. Further comparison showed that miR-455-5p was specifically differentially expressed in exosomes, and miR-1255a was commonly expressed in exosomal and original cells samples. miR-455-5p could interact with CDKN1B to influence cell cycle process and miR-1255a could regulate SMAD4 to participate in TGF-β signaling pathway. High expressed miR-455-5p (basal-like) and miR-1255a (overall) were associated with poor overall survival, while the high expression of their target genes was associated with excellent overall, recurrence-free or distant metastasis-free survival. In conclusion, the present study preliminarily indicates that exosomal miR-455-5p and miR-1255a may be novel therapeutic targets for BC.", "claims": [{"id": "claim-method", "statement": "The DEMs between normal mammary epithelial cells and breast cancer cells in exosomal and original cell samples were identified using the EdgeR package (version 3.24.4; http://www.bioconductor.org/packages/release/bioc/html/edgeR.html) [19] of R software.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31763681", "locator": "sections[4] \"Data preprocessing and identification of DEMs\" paragraph 2", "quote": "The DEMs between normal mammary epithelial cells and breast cancer cells in exosomal and original cell samples were identified using the EdgeR package (version 3.24.4; http://www.bioconductor.org/packages/release/bioc/html/edgeR.html) [19] of R software."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE83669 dataset contained six samples, including exosomal samples of two human breast cancer cells (MCF7 and MDA-MB-231) and one normal mammary epithelial cell line (MCF10) as well as their original cells, which were obtained on Illumina MiSeq platform (GPL15520).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31763681", "locator": "sections[3] \"Data collection\" paragraph 2", "quote": "GSE83669 dataset contained six samples, including exosomal samples of two human breast cancer cells (MCF7 and MDA-MB-231) and one normal mammary epithelial cell line (MCF10) as well as their original cells, which were obtained on Illumina MiSeq platform (GPL15520)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:31763681"], "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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expressed miRNAs in two datasets", "rows": [["", "GSE83669", "GSE50429"], ["", "ID", "logFC", "P-value", "ID", "logFC", "P-value"], ["Exosomes", "hsa-miR-1255a", "−1.75", "5.36E-03", "hsa-miR-1255a", "1.22", "4.90E-02"], ["", "hsa-miR-199b-5p", "3.03", "1.91E-03", "hsa-miR-199b-5p", "4.74", "4.90E-02"], ["", "hsa-miR-296-5p", "−3.42", "3.06E-03", "hsa-miR-296-5p", "-3.03", "4.46E-03"], ["", "hsa-miR-34c-3p", "1.22", "4.90E-02", "hsa-miR-34c-3p", "-2.79", "6.8E-03"], ["", "hsa-miR-409-3p", "1.16", "1.31E-02", "hsa-miR-409-3p", "3.31", "4.01E-02"], ["", "hsa-miR-455-3p", "2.72", "3.45E-03", "hsa-miR-455-3p", "6.65", "4.90E-02"], ["", "hsa-miR-455-5p", "3.14", "1.05E-03", "hsa-miR-455-5p", "6.03", "4.90E-02"], ["", "hsa-miR-548k", "−4.13", "7.66E-04", "hsa-miR-548k", "-1.12", "1.77E-03"], ["", "hsa-miR-641", "−1.33", "4.90E-02", "hsa-miR-641", "1.50", "4.90E-02"], ["Original", "hsa-miR-1255a", "1.09", "3.07E-02", "hsa-miR-1255a", "1.33", "2.89E-02"], ["", "hsa-miR-1291", "4.09", 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"section[12]/table-wrap[1]#T2", "version": null, "note": "Function enrichment for mRNAs in the miRNA–mRNA interaction network", "structure": {"pmcid": "PMC6970063", "section_index": 12, "section_title": "Function enrichment for target genes of DEMs", "row_count": 35, "column_count": 4}, "table": {"label": "Table 2", "caption": "Function enrichment for mRNAs in the miRNA–mRNA interaction network", "rows": [["Category", "Term", "P-value", "Genes"], ["GO", "GO:0042127∼regulation of cell proliferation", "5.38E-15", "CSF3, PDGFA, FOXM1, PTGS1, BMPR2, GJA1, ZEB1, PTEN, CTNNB1, VDR, IGF1R, KRT5, HMOX1, IFNG, TGM2, IL1B, IL6, FLT1, SMAD4, MFGE8, RB1, FOXP3, SIRT1, HHEX, CDKN1B, HIF1A, MDM2, MDM4, FABP7"], ["", "GO:0010604∼positive regulation of macromolecule metabolic process", "7.60E-10", "IL6, PDGFA, FOXA1, BMPR2, SMAD4, FHL2, GJA1, RB1, ZEB1, FOXP3, TP73, CTNNB1, AKT1, HHEX, IGF1R, EP300, HIF1A, HMOX1, IFNG, MDM2, IL1B, H2AFX, BARD1, ACVR1"], ["", "GO:0009725∼response to hormone stimulus", "4.56E-09", "IL6, PDGFA, PTGS1, FHL2, MFGE8, STXBP4, PTEN, CTNNB1, AKT1, IGF1R, PDPK1, EP300, BCHE, HMOX1, IL1B, SPP1"], ["", "GO:0009719∼response to endogenous stimulus", "1.72E-08", "IL6, PDGFA, PTGS1, FHL2, MFGE8, STXBP4, PTEN, CTNNB1, AKT1, IGF1R, PDPK1, EP300, BCHE, HMOX1, IL1B, SPP1"], ["", "GO:0008285∼negative regulation of cell proliferation", "3.07E-08", "IL6, SMAD4, GJA1, RB1, ZEB1, FOXP3, PTEN, VDR, CDKN1B, KRT5, HMOX1, IFNG, IL1B, MDM4, FABP7"], ["", "GO:0051173∼positive regulation of nitrogen compound metabolic process", "4.18E-08", "IL6, PDGFA, FOXA1, SMAD4, FHL2, RB1, ZEB1, FOXP3, TP73, CTNNB1, AKT1, HHEX, IGF1R, EP300, HIF1A, IFNG, IL1B, H2AFX, ACVR1"], ["", "GO:0010033∼response to organic substance", "4.18E-08", "IL6, PDGFA, RBM3, PTGS1, FHL2, MFGE8, STXBP4, PTEN, CTNNB1, AKT1, IGF1R, PDPK1, EP300, TFRC, BCHE, HMOX1, IFNG, CASP8, IL1B, SPP1"], ["", "GO:0010557∼positive regulation of macromolecule biosynthetic process", "5.28E-08", "IL6, PDGFA, FOXA1, SMAD4, FHL2, RB1, ZEB1, FOXP3, TP73, CTNNB1, AKT1, HHEX, IGF1R, EP300, HIF1A, HMOX1, IFNG, IL1B, ACVR1"], ["", "GO:0031328∼positive regulation of cellular biosynthetic process", "1.06E-07", "IL6, PDGFA, FOXA1, SMAD4, FHL2, RB1, ZEB1, FOXP3, TP73, CTNNB1, AKT1, HHEX, IGF1R, EP300, HIF1A, HMOX1, IFNG, IL1B, ACVR1"], ["", "GO:0009891∼positive regulation of biosynthetic process", "1.32E-07", "IL6, PDGFA, FOXA1, SMAD4, FHL2, RB1, ZEB1, FOXP3, TP73, CTNNB1, AKT1, HHEX, IGF1R, EP300, HIF1A, HMOX1, IFNG, IL1B, ACVR1"], ["", "GO:0012501∼programmed cell death", "6.40E-07", "IL6, CADM1, GJA1, SIRT1, PTEN, TP73, CTNNB1, AKT1, SFRP5, TNFSF10, EP300, CDKN1B, IFNG, CASP8, TGM2, IL1B, MDM4"], ["", "GO:0042325∼regulation of phosphorylation", "7.01E-07", "IL6, FLT1, PDGFA, BMPR2, SMAD4, RB1, LPAR1, PTEN, TP73, AKT1, PDPK1, CDKN1B, IFNG, IL1B, BARD1"], ["", "GO:0008219∼cell death", "1.12E-06", "IL6, CADM1, GJA1, SIRT1, PTEN, TP73, CTNNB1, AKT1, SFRP5, TNFSF10, EP300, CDKN1B, HMOX1, IFNG, CASP8, TGM2, IL1B, MDM4"], ["", "GO:0042981∼regulation of apoptosis", "1.13E-06", "IL6, CADM1, SIRT1, PTEN, TP73, AKT1, VDR, IGF1R, TNFSF10, CDKN1B, SFRP1, HMOX1, IFNG, CASP8, TGM2, IL1B, TERT, BARD1, ACVR1"], ["", "GO:0051174∼regulation of phosphorus metabolic process", "1.13E-06", "IL6, FLT1, PDGFA, BMPR2, SMAD4, RB1, LPAR1, PTEN, TP73, AKT1, PDPK1, CDKN1B, IFNG, IL1B, BARD1"], ["", "GO:0019220∼regulation of phosphate metabolic process", "1.13E-06", "IL6, FLT1, PDGFA, BMPR2, SMAD4, RB1, LPAR1, PTEN, TP73, AKT1, PDPK1, CDKN1B, IFNG, IL1B, BARD1"], ["", "GO:0016265∼death", "1.23E-06", "IL6, CADM1, GJA1, SIRT1, PTEN, TP73, CTNNB1, AKT1, SFRP5, TNFSF10, EP300, CDKN1B, HMOX1, IFNG, CASP8, TGM2, IL1B, MDM4"], ["", "GO:0043067∼regulation of programmed cell death", "1.30E-06", "IL6, CADM1, SIRT1, PTEN, TP73, AKT1, VDR, IGF1R, TNFSF10, CDKN1B, SFRP1, HMOX1, IFNG, CASP8, TGM2, IL1B, TERT, BARD1, ACVR1"], ["", "GO:0010941∼regulation of cell death", "1.37E-06", "IL6, CADM1, SIRT1, PTEN, TP73, AKT1, VDR, IGF1R, TNFSF10, CDKN1B, 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(Exosome: MCF7 versus MCF10A) [24]", "miR-1255a", "2.09", "1.80", "", ""], ["", "miR-455-5p", "3.05", "2.97", "", ""], ["GSE60714 (Exosome, MDA-MB231 versus MCF10A) [24]", "miR-1255a", "", "", "2.14", "0.02"], ["", "miR-455-5p", "", "", "3.19", "0.02"], ["GSE45666 (tissue)", "miR-1255a", "", "", "5.27", "7.14E-03"], ["TCGA (tissue)", "miR-1255a", "0.80 ± 0.73", "0.67 ± 0.51", "", "0.509"], ["", "miR-455", "6.93 ± 1.19", "6.80 ± 0.64", "", "<0.001"], ["", "SMAD4", "10.47± 0.53", "11.13±0.27", "", "<0.001"], ["", "CDKN1B (basal-like)", "43.84 (11.39-81.35)", "63.55 (36.69-104.94)", "", "<0.001"]], "row_count": 10, "column_count": 6, "numeric_cells": 32, "header_rows": 1, "locator": "section[13]/table-wrap[1]#T3"}}, {"id": "asset:table:pmid:31763681:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1f352cb8fc4fa459c287b64d657cee5d203d1adc04d6bf8dbf759ee887b98b0f", "bytes": 1449, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#T4", "version": null, "note": "Clinical association of differentially expressed miRNAs and their target genes", "structure": {"pmcid": "PMC6970063", "section_index": 13, "section_title": "Validation of crucial DEMs and mRNAs using another datasets", "row_count": 11, "column_count": 9}, "table": {"label": "Table 4", "caption": "Clinical association of differentially expressed miRNAs and their target genes", "rows": [["Query", "P-value"], ["", "miR-1255a", "miR-1291", "miR-455", "miR-199b", "IL1B", "SMAD4", "FOXP3", "CDKN1B"], ["Pathologic_stage (Kruskal–Wallis Test)", "3.98E-01", "6.00E-01", "2.60E-02", "2.83E-01", "2.64E-04", "1.01E-01", "8.08E-01", "7.92E-01"], ["Pathology_T_stage (Kruskal–Wallis Test)", "2.90E-01", "3.48E-01", "2.58E-02", "3.67E-03", "1.22E-05", "4.17E-03", "6.95E-03", "1.52E-01"], ["Pathology_N_stage (Kruskal–Wallis Test)", "2.43E-01", "1.48E-01", "1.10E-03", "3.26E-02", "5.96E-03", "1.48E-01", "4.50E-01", "5.46E-01"], ["Pathology_M_stage (Wilcox Test)", "6.95E-01", "3.14E-01", "4.37E-01", "6.35E-01", "4.26E-02", "6.08E-01", "3.68E-01", "5.55E-01"], ["PAM50 (Kruskal–Wallis Test)", "5.17E-04", "9.84E-03", "2.76E-35", "3.71E-01", "1.51E-07", "2.77E-14", "1.23E-16", "1.12E-15"], ["ER.Status (Wilcox Test)", "1.38E-01", "2.36E-01", "3.83E-04", "7.34E-01", "2.16E-01", "5.34E-01", "1.50E-02", "2.64E-04"], ["PR.Status (Wilcox Test)", "2.05E-01", "3.23E-01", "3.42E-02", "3.52E-01", "3.94E-01", "2.46E-01", "9.99E-03", "2.38E-03"], ["HER2.Status (Wilcox Test)", "2.10E-01", "5.18E-01", "1.23E-02", "7.81E-03", "3.78E-01", "7.96E-03", "3.00E-02", "6.23E-02"], ["Radiation_therapy (Wilcox Test)", "1.15E-01", "8.01E-01", "9.82E-01", "1.11E-01", "7.37E-01", "3.28E-01", "6.12E-02", "4.98E-01"]], "row_count": 11, "column_count": 9, "numeric_cells": 77, "header_rows": 2, "locator": "section[13]/table-wrap[2]#T4"}}], "gaps": ["asset:data:geo:GSE45666 not downloaded", "asset:data:geo:GSE45666 licence not read", "asset:data:geo:GSE50429 not downloaded", "asset:data:geo:GSE50429 licence not read", "asset:data:geo:GSE60714 not downloaded", "asset:data:geo:GSE60714 licence not read", "asset:data:geo:GSE83669 not downloaded", "asset:data:geo:GSE83669 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "edger", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The DEMs between normal mammary epithelial cells and breast cancer cells in exosomal and original cell samples were identified using the EdgeR package (version 3.24.4; 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