Identification of exosomal and non‑exosomal microRNAs associated with the drug resistance of ovarian cancer.

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The current study aimed to analyze the drug resistance‑associated exosomal miRNAs in original OC cells and their derived exosomes using microarray data downloaded from the Gene Expression Omnibus database (series GSE76449). The chemosensitive OC cell lines SKOV3_ip1, A2780_PAR and HEYA8, as well as the chemoresistant cell lines SKOV3_TR, A2780_CP20 and HEYA8_MDR, were investigated. Differentially expressed miRNAs (DE‑miRNAs) were identified using the limma method, and their mRNA targets were predicted using the miRWalk and LinkedOmics database. Functions of target genes were analyzed with DAVID tool, while TCGA data were used to explore the survival association of identified miRNAs. According to the results, 28 DE‑miRNAs were found to be common in exosomal and original samples of A2780_CP20 cells, among which the functions of 5 miRNAs were predicted (including miR‑146b‑5p, miR‑509‑5p, miR‑574‑3p, miR‑574‑5p and miR‑760). In addition, 16 and 35 DE‑miRNAs were detected for HEYA8_MDR and SKOV3_TR, respectively, with the functions of 4 of these miRNAs predicted for each cell line (HEYA8_MDR: miR‑30a‑3p, miR‑30a‑5p, miR‑612 and miR‑617; SKOV3_TR: miR‑193a‑5p, miR‑423‑3p, miR‑769‑5p and miR‑922). It was also reported that miR‑183‑5p was the only one common miRNA among the three cell lines. Furthermore, miR‑574‑3p, miR‑30a‑5p and miR‑922 may regulate CUL2 to mediate HIF‑1 cancer signaling pathway, while miR‑183‑5p may modulate MECP2, similar to miR‑760, miR‑30a‑5p and miR‑922, to influence cell proliferation. Finally, the downregulated miR‑612 may promote the expression of TEAD3 via the Hippo signaling pathway, and this miRNA was associated with poor prognosis. In conclusion, the findings of the present study suggested several underlying miRNA targets for improving the chemotherapy sensitivity of OC.", "claims": [{"id": "claim-method", "statement": "DE-miRNAs between chemosensitive and chemoresistant cells were identified using the limma method (also known as Linear Models for Microarray data) (14) in the Bioconductor R package (version 3.4.1; http://www.r-project.org/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30864705", "locator": "sections[5] \"Data normalization and identification of differentially expressed miRNAs (DE-miRNAs)\" paragraph 3", "quote": "DE-miRNAs between chemosensitive and chemoresistant cells were identified using the limma method (also known as Linear Models for Microarray data) (14) in the Bioconductor R package (version 3.4.1; http://www.r-project.org/)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data GSE76449 were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30864705", "locator": "sections[18] \"Availability of data and materials\" paragraph 2", "quote": "The microarray data GSE76449 were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/)."}], "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:30864705"], "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:GSE76449"], "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:GSE76449"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30864705", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3892/mmr.2019.10008", "sha256": "sha256:302c2b294e9902c4069650309e895ba412fe883d5e9514e64873483f3ebb3a5e", "bytes": 28311, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3892/mmr.2019.10008", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6471492", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE76449", "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=GSE76449", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE76449", "version": null, "note": "The microarray data GSE76449 were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The microarray data GSE76449 were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2024789", "GSM2024790", "GSM2024791", "GSM2024792", "GSM2024793", "GSM2024794", "GSM2024795", "GSM2024796", "GSM2024797", "GSM2024798", "GSM2024799", "GSM2024800", "GSM2024801", "GSM2024802", "GSM2024803", "GSM2024804", "GSM2024805", "GSM2024806", "GSM2024807", "GSM2024808", "GSM2024809", "GSM2024810", "GSM2024811", "GSM2024812", "GSM2024813", "GSM2024814", "GSM2024815", "GSM2024816"], "sample_count": 28, "group_sizes": null, "group_sizes_basis": null, "platform": "19117", "taxon": "Homo sapiens; synthetic construct", "title": "miRNA Expression Data from Ovarian Cancer Exosomes and Cells of Origin", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE76449 not downloaded", "asset:data:geo:GSE76449 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "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": "DE-miRNAs between chemosensitive and chemoresistant cells were identified using the limma method (also known as Linear Models for Microarray data) (14) in the Bioconductor R package (version 3.4.1; http://www.r-project.org/)."}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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