Exploring the Molecular Mechanism of lncRNA-miRNA-mRNA Networks in Non-Syndromic Cleft Lip with or without Cleft Palate.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34938111", "kind": "science-record", "revision": 5, "content_hash": "sha256:0d953e791ecda70efafa812349b66f8d4960ffb600dce942e27263cb5fbb8d78", "created_at": "2026-11-01T17:36:38Z", "updated_at": "2026-11-01T22:48:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring the Molecular Mechanism of lncRNA-miRNA-mRNA Networks in Non-Syndromic Cleft Lip with or without Cleft Palate.", "doi": "10.2147/IJGM.S339504", "pmid": "34938111", "authors": ["Xiangpu Wang", "Siyuan Guo", "Xinli Zhou", "Yupei Wang", "Ting Zhang", "Renji Chen"], "journal": "International journal of general medicine", "year": 2021, "abstract": "BACKGROUND: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common craniofacial birth defect. Growing evidence has demonstrated the competing endogenous RNA (ceRNA) hypothesis has played a role in the pathogenesis of NSCL/P. Here, we identified the important lncRNAs in NSCL/P and constructed a ceRNA regulatory network to predict their underlying functional mechanism.\nMETHODS: Total RNA isolated from the peripheral blood samples were analyzed by the Human Clariom D Affymetrix platform and differentially expressed genes (DEGs) were identified. Using the limma package in R software, DEGs in the expression profile of GSE42589 were identified from Gene Expression Omnibus (GEO) database. Co-differentially expressed lncRNAs (co-DElncRNAs) were used to predict the microRNAs that may bind to them. Co-differentially expressed mRNAs (co-DEmRNAs) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The hub genes were screened using the cytohubba plug-in in Cytoscape. A ceRNA network was built to investigate the molecular mechanism underlying the etiology of NSCL/P. The expression levels of lncRNAs, miRNAs, and mRNAs in the network were assessed by quantitative real-time polymerase chain reaction (qRT-PCR).\nRESULTS: We found 116 DElncRNAs and 2955 DEmRNAs from the GSE42589 dataset, and 2626 DElncRNAs and 2771 DEmRNAs from the Human Clariom D gene chip. A network of co-DEmRNAs containing 3712 edges and 621 nodes were identified by PPI analysis. A ceRNA regulatory network comprising lncRNA USP17L6P, hsa-miR-449c-5p, and MYC was established. qRT-PCR results revealed significantly lower expression levels of lncRNA USP17L6P and c-Myc in NSCL/P tissues, while the expression level of hsa-miR-449c-5p was higher as compared to control samples (p < 0.05).\nCONCLUSION: The identified lncRNAs and the established ceRNA regulatory network provide novel insight into the pathogenesis of NSCL/P, therefore hold great promise in NSCL/P management in clinical practice.", "claims": [{"id": "claim-method", "statement": "DEGs were identified by comparing NSCL/P and normal samples via the R limma package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34938111", "locator": "sections[5] \"Acquisition and Processing of Gene Expression Data in Public Datasets\" paragraph 2", "quote": "DEGs were identified by comparing NSCL/P and normal samples via the R limma package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The publical dataset generated and analyzed in this study is available in the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/). The dataset of Affymetrix Clariom D array used and analyzed during the current study is available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34938111", "locator": "sections[19] \"Data Sharing Statement\" paragraph 2", "quote": "The publical dataset generated and analyzed in this study is available in the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/). The dataset of Affymetrix Clariom D array used and analyzed during the current study is available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 116 DElncRNAs and 2955 DEmRNAs from GSE42589 and 2626 DElncRNAs and 2771 DEmRNAs from the Human Clariom D gene chip, and established a ceRNA regulatory network comprising lncRNA USP17L6P, hsa-miR-449c-5p, and MYC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34938111", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We found 116 DElncRNAs and 2955 DEmRNAs from the GSE42589 dataset, and 2626 DElncRNAs and 2771 DEmRNAs from the Human Clariom D gene chip."}, {"asset": "source:pmid:34938111", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A ceRNA regulatory network comprising lncRNA USP17L6P, hsa-miR-449c-5p, and MYC was established."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 116 DElncRNAs and 2955 DEmRNAs from GSE42589 and 2626 DElncRNAs and 2771 DEmRNAs from the Human Clariom D gene chip, and established a ceRNA regulatory network comprising lncRNA USP17L6P, hsa-miR-449c-5p, and MYC.", "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:34938111"], "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:GSE42589"], "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:GSE42589"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34938111", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S339504", "sha256": "sha256:9885a52bbec11fd5e1ee5f5acfba3cb9d6fe67d051aa1e69710f031d0c4dfa53", "bytes": 34833, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/IJGM.S339504", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8687630", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE42589", "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=GSE42589", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE42589", "version": null, "note": "The publical dataset generated and analyzed in this study is available in the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/). The dataset of Affymetrix Clariom D array used and analyzed during the current study is available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The publical dataset generated and analyzed in this study is available in the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/). The dataset of Affymetrix Clariom D array used and analyzed during the current study is available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1045517", "GSM1045518", "GSM1045519", "GSM1045520", "GSM1045521", "GSM1045522", "GSM1045523", "GSM1045524", "GSM1045525", "GSM1045526", "GSM1045527", "GSM1045528", "GSM1045529"], "sample_count": 13, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Susceptibility to DNA damage as a molecular mechanism for non-syndromic cleft lip and palate", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE42589 not downloaded", "asset:data:geo:GSE42589 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": "DEGs were identified by comparing NSCL/P and normal samples via the R limma package."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "PPI"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}], "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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