Construction of circRNA-Based ceRNA Network to Reveal the Role of circRNAs in the Progression and Prognosis of Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33719338", "kind": "science-record", "revision": 6, "content_hash": "sha256:f1a6478bf6c3bd018a3fe1ef70616142bfcf9b7cf76d9a71b677707c29818fe2", "created_at": "2026-11-01T15:41:28Z", "updated_at": "2026-11-01T21:24:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of circRNA-Based ceRNA Network to Reveal the Role of circRNAs in the Progression and Prognosis of Hepatocellular Carcinoma.", "doi": "10.3389/fgene.2021.626764", "pmid": "33719338", "authors": ["Rong Deng", "Xiaohan Cui", "Yuxiang Dong", "Yanqiu Tang", "Xuewen Tao", "Shuyu Wang", "Jincheng Wang", "Lin Chen"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "BACKGROUND: Circular RNAs (circRNAs) are now under hot discussion as novel promising biomarkers for patients with hepatocellular carcinoma (HCC). The purpose of our study is to identify several competing endogenous RNA (ceRNA) networks related to the prognosis and progression of HCC and to further investigate the mechanism of their influence on tumor progression.\nMETHODS: First, we obtained gene expression data related to liver cancer from The Cancer Genome Atlas (TCGA) database (http://www.portal.gdc.cancer.gov/), including microRNA (miRNA) sequence, RNA sequence, and clinical information. A co-expression network was constructed through the Weighted Correlation Network Analysis (WGCNA) software package in R software. The differentially expressed messenger RNAs (DEmRNAs) in the key module were analyzed with the Database for Annotation Visualization and Integrated Discovery (DAVID) (https://david.ncifcrf.gov/summary.jsp) to perform functional enrichment analysis including Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The data of miRNA expression and clinical information downloaded from TCGA were utilized for survival analysis to detach the prognostic value of the DEmiRNAs of the key module.\nRESULTS: The 201 differentially expressed miRNAs (DEmiRNAs) and 3,783 DEmRNAs were preliminarily identified through differential expression analysis. The co-expression networks of DEmiRNAs and DEmRNAs were constructed with WGCNA. Further analysis confirmed four miRNAs in the most significant module (blue module) were associated with the overall survival (OS) of patients with liver cancer, including hsa-miR-92b-3p, hsa-miR-122-3p, hsa-miR-139-5p, and hsa-miR-7850-5p. DAVID was used for functional enrichment analysis of 286 co-expressed mRNAs. The GO analysis results showed that the top enriched GO terms were oxidation-reduction process, extracellular exosome, and iron ion binding. In KEGG pathway analysis, the top three enriched terms included metabolic pathways, fatty acid degradation, and valine, leucine, and isoleucine degradation. In addition, we intersected the miRNA-mRNA interaction prediction results with the differentially expressed and prognostic mRNAs. We found that hsa-miR-92b-3p can be related to CPEB3 and ACADL. By overlapping the data of predicted circRNAs by circBank and differentially expressed circRNAs of GSE94508, we screened has_circ_0077210 as the upstream regulatory molecule of hsa-miR-92b-3p. Hsa_circ_0077210/hsa-miR-92b-3p/cytoplasmic polyadenylation element binding protein-3 (CPEB3) and acyl-Coenzyme A dehydrogenase, long chain (ACADL) were validated in HCC tissue.\nCONCLUSION: Our research provides a mechanistic elucidation of the unknown ceRNA regulatory network in HCC. Hsa_circ_0077210 might serve a momentous therapeutic role to restrain the occurrence and development of HCC.", "claims": [{"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33719338", "locator": "sections[21] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE94508"], "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": {"p_value": "ndition of the log-rank P value < 0"}, "inputs": ["data:geo:GSE94508"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33719338", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.626764", "sha256": "sha256:cc13b767952cc11c59a3b5848571312e65bf334f7271a22a2735b7aa92551ac9", "bytes": 44261, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.626764", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7953168", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE94508", "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=GSE94508", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE94508", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2477191", "GSM2477192", "GSM2477193", "GSM2477194", "GSM2477195", "GSM2477196", "GSM2477197", "GSM2477198", "GSM2477199", "GSM2477200"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "19978", "taxon": "Homo sapiens", "title": "circRNA expression profiles for 10 human samples derived from patients with hepatocellular carcinoma", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33719338:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4312b5178e3c07bf9c08f407faaee18aac0c4c9b53f6492e406349a9d5470106", "bytes": 907, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#T1", "version": null, "note": "22 survival-related genes in brown and yellow module.", "structure": {"pmcid": "PMC7953168", "section_index": 17, "section_title": "Screen of miRNA–mRNA Interactions and Pathway Analysis of Target mRNAs", "row_count": 23, "column_count": 2}, "table": {"label": "TABLE 1", "caption": "22 survival-related genes in brown and yellow module.", "rows": [["Gene", "KM (P-value)"], ["N4BP2L1", "0.0231917680013911"], ["C6", "0.0324979505945558"], ["DMGDH", "0.00345549731847261"], ["ACADL", "0.0458976763753126"], ["CYP7A1", "0.015599256837466"], ["MANF", "0.0354210475561331"], ["SARDH", "0.0458207466346884"], ["TUBE1", "0.0171553602956993"], ["ANXA10", "0.0281889814075095"], ["SLC38A4", "0.0209045132009409"], ["C8B", "0.0298561967458564"], ["LPA", "0.0172195797768141"], ["MAT1A", "0.0461625356948938"], ["ADH4", "0.00572238509386069"], ["SLC10A1", "0.025877998862526"], ["FNIP2", "0.0474647059410264"], ["CYP4F2", "0.0298914997690577"], ["TTC36", "0.0224862889024342"], ["ADRA1A", "0.0466515861358356"], ["GYS2", "0.0334809963912731"], ["ABAT", "0.0259103935446722"], ["CPEB3", "0.0403726764983748"]], "row_count": 23, "column_count": 2, "numeric_cells": 26, "header_rows": 1, "locator": "section[17]/table-wrap[1]#T1"}}], "gaps": ["asset:data:geo:GSE94508 not downloaded", "asset:data:geo:GSE94508 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {"p_value": "ndition of the log-rank P value < 0"}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}], "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": ["logrank_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: log_rank_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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