← All .science files
pmid:34306017
A Novel circRNA-miRNA-mRNA Hub Regulatory Network in Lung Adenocarcinoma.
Haiwei Zuo · Xia Li · Xixi Zheng · Qiuwen Sun · Qianqian Yang · Yong Xin
Frontiers in genetics · 2021 doi:10.3389/fgene.2021.673501
Paper
complete
Experiment
partial
Data
partial
Analysis
complete
Execution
absent
Execution evidence has not yet been added to this .science file. Explore its methods, data and open questions to plan the next step.
Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
paper object · 10 fields
authors array · 6 items
claims array · 2 items
[0] object · 6 fields
[1] object · 6 fields
evidence array · 1 item
[0] object · 3 fields
gaps array · 0 items
experiment object · 8 fields
steps array · 3 items
[0] object · 13 fields
parameters object · 0 fields
inputs array · 1 item
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
[1] object · 13 fields
parameters object · 0 fields
inputs array · 0 items
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
[2] object · 13 fields
parameters object · 0 fields
inputs array · 0 items
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
materials array · 0 items
instruments array · 0 items
reagents array · 0 items
conditions object · 0 fields
gaps array · 1 item
data object · 3 fields
assets array · 3 items
[0] object · 15 fields
structure object · 4 fields
[1] object · 16 fields
structure object · 5 fields
table object · 8 fields
rows array · 6 items
[0] array · 8 items
[1] array · 8 items
[2] array · 8 items
[3] array · 8 items
[4] array · 8 items
[5] array · 8 items
[2] object · 16 fields
structure object · 5 fields
table object · 8 fields
rows array · 9 items
[0] array · 7 items
[1] array · 7 items
[2] array · 7 items
[3] array · 7 items
[4] array · 7 items
[5] array · 7 items
[6] array · 7 items
[7] array · 7 items
[8] array · 7 items
gaps array · 0 items
analysis object · 4 fields
methods array · 1 item
[0] object · 10 fields
dsl_operations array · 1 item
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
requirements array · 1 item
[0] object · 6 fields
assay_families array · 9 items
gaps array · 0 items
readiness object · 8 fields
axes object · 3 fields
method object · 5 fields
required_operations array · 1 item
missing_operations array · 0 items
capability object · 4 fields
data object · 6 fields
accessions array · 0 items
resolved_accessions array · 0 items
statements array · 1 item
can_run object · 3 fields
dsl_operations array · 1 item
assets array · 3 items
steps array · 1 item
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
gaps array · 1 item
review object · 5 fields
machine_critique object · 5 fields
reader object · 5 fields
evidence_check object · 2 fields
usage object · 3 fields
stages array · 1 item
[0] object · 4 fields
gaps array · 3 items
provenance object · 7 fields
entities array · 3 items
activities array · 3 items
[0] object · 4 fields
used array · 3 items
[0] object · 3 fields
[1] object · 3 fields
[2] object · 3 fields
[1] object · 4 fields
agents array · 2 items
lineage object · 4 fields
gaps array · 5 items
assays array · 2 items
[0] object · 11 fields
required_operations array · 0 items
source_hashes object · 1 field
evidence array · 1 item
[1] object · 11 fields
required_operations array · 1 item
source_hashes object · 1 field
evidence array · 1 item
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34306017", "kind": "science-record", "revision": 6, "content_hash": "sha256:22e208d00beca9099c0c18dcfcfb8ce817ce67e467f54ccea51b4c810fc451e0", "created_at": "2026-11-01T15:41:45Z", "updated_at": "2026-11-01T21:25:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Novel circRNA-miRNA-mRNA Hub Regulatory Network in Lung Adenocarcinoma.", "doi": "10.3389/fgene.2021.673501", "pmid": "34306017", "authors": ["Haiwei Zuo", "Xia Li", "Xixi Zheng", "Qiuwen Sun", "Qianqian Yang", "Yong Xin"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "The growing evidence suggests that circular RNAs (circRNAs) have significant associations with tumor occurrence and progression, yet the regulatory mechanism of circRNAs in lung adenocarcinoma (LUAD) remains unclear. This study clarified the potentially regulatory network and functional mechanism of circRNAs in LUAD. The expression data of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) were obtained from the Gene Expression Omnibus (GEO) database. Relying on GSE101586, GSE101684, and GSE112214, we identified differentially expressed circRNAs (DEcircRNAs). Depending on GSE135918 and GSE32863, we screened out differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs), respectively. Then, a novel competing endogenous RNA (ceRNA) regulatory network related to LUAD was constructed. We also revealed biological processes and signal pathways regulated by these DEcircRNAs. Based on gene expression data and survival information of LUAD patients in The Cancer Genome Atlas (TCGA) and GEO, we implemented survival analysis to select DEmRNAs related to prognosis and build a novel circRNA-miRNA-mRNA hub regulatory network. Meanwhile, quantitative real-time PCR (qRT-PCR) was utilized to validate DEcircRNAs in the ceRNA hub regulatory network. As a result, a total of 8 DEcircRNAs, 19 DEmiRNAs, and 85 DEmRNAs were identified. The novel ceRNA regulatory network included 5 circRNAs, 8 miRNAs, and 22 mRNAs. The final ceRNA hub regulatory network contained two circRNAs, two miRNAs, and two mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the five DEcircRNAs may affect LUAD onset and progression through Wnt signaling pathway and Hippo signaling pathway. All in all, this study revealed the regulatory network and functional mechanism of circRNA-related ceRNAs in LUAD.", "claims": [{"id": "claim-method", "statement": "The log-rank test was applied to achieve statistical verification (p < 0.05).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34306017", "locator": "sections[9] \"Survival Analysis, RNA Extraction, and qRT-PCR\" paragraph 2", "quote": "The log-rank test was applied to achieve statistical verification (p < 0.05)."}], "state": "complete"}, {"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:34306017", "locator": "sections[16] \"Data Availability Statement\" paragraph 2", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:34306017"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34306017", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.673501", "sha256": "sha256:f13acbbf7dfcf068e8a1ec4424d186005998fe3ef38272781bb5dd16b4994919", "bytes": 29417, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.673501", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8292838", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:34306017:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3ea4b3bd71dd101a8c67a04b4cbb44b09902c658c19b750d57ce2b026be9648f", "bytes": 669, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#T1", "version": null, "note": "Basic information of five microarray datasets from the GEO database.", "structure": {"pmcid": "PMC8292838", "section_index": 11, "section_title": "Identification of DEcircRNAs, DEmiRNAs, and DEmRNAs in LUAD", "row_count": 6, "column_count": 8}, "table": {"label": "TABLE 1", "caption": "Basic information of five microarray datasets from the GEO database.", "rows": [["Data source", "Series", "Platform", "Author", "Year", "Area", "Sample size (T/N)", "No. of RNAs"], ["circRNA", "GSE101586", "GPL19978", "Qiu", "2019", "China", "5/5", "4,425"], ["circRNA", "GSE101684", "GPL21825", "Xu", "2019", "China", "4/4", "9,114"], ["circRNA", "GSE112214", "GPL19978", "Dong", "2019", "China", "3/3", "4,407"], ["miRNA", "GSE135918", "GPL18058", "Jiang", "2020", "China", "5/5", "3,551"], ["mRNA", "GSE32863", "GPL6884", "Selamat", "2019", "United States", "58/58", "48,803"]], "row_count": 6, "column_count": 8, "numeric_cells": 25, "header_rows": 1, "locator": "section[11]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:34306017:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c922d0348974145ac30594d093453e8e9590188f99ad1d3fb52924fd4d2d68f8", "bytes": 982, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[2]#T2", "version": null, "note": "Basic characteristics of eight DEcircRNAs.", "structure": {"pmcid": "PMC8292838", "section_index": 11, "section_title": "Identification of DEcircRNAs, DEmiRNAs, and DEmRNAs in LUAD", "row_count": 9, "column_count": 7}, "table": {"label": "TABLE 2", "caption": "Basic characteristics of eight DEcircRNAs.", "rows": [["circRNA ID", "Position", "Genomic length", "Strand", "Best transcript", "Gene symbol", "Regulation"], ["hsa_circ_0072088", "chr5:32379220-32388780", "9,560", "−", "NM_016107", "ZFR", "Up"], ["hsa_circ_0000520", "chr14:20811436-20811559", "123", "−", "NR_002312", "RPPH1", "Up"], ["hsa_circ_0043256", "chr17:35604934-35609962", "5,028", "−", "NM_198839", "ACACA", "Down"], ["hsa_circ_0072309", "chr5:38523520-38530768", "7,248", "−", "NM_001127671", "LIFR", "Down"], ["hsa_circ_0004789", "chr17:62587201-62594608", "7,407", "−", "NM_022739", "SMURF2", "Down"], ["hsa_circ_0003162", "chr7:33185853-33217203", "31,350", "+", "NM_198428", "BBS9", "Down"], ["hsa_circ_0069244", "chr4:16587544-16760883", "173,339", "−", "NM_001130834", "LDB2", "Down"], ["hsa_circ_0049271", "chr19:10610070-10610756", "686", "−", "NM_203500", "KEAP1", "Down"]], "row_count": 9, "column_count": 7, "numeric_cells": 32, "header_rows": 1, "locator": "section[11]/table-wrap[2]#T2"}}], "gaps": []}, "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": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The log-rank test was applied to achieve statistical verification (p < 0.05)."}}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "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. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["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."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["logrank_test"], "assets": ["source:pmid:34306017", "asset:table:pmid:34306017:1", "asset:table:pmid:34306017:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:42:43Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 23407, "completion_tokens": 2328, "cached_tokens": 784}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:34306017", "type": "paper", "label": "pmid:34306017"}, {"id": "source:pmid:34306017", "type": "manuscript", "label": "PMID 34306017 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34306017", "type": "paper", "label": "pmid:34306017"}, {"id": "source:pmid:34306017", "type": "manuscript", "label": "PMID 34306017 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34306017", "type": "extraction", "used": ["source:pmid:34306017"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:34306017", "parent_hash": "sha256:6a007e8f70893a02f4d0206170414def18911046f421e29dcab3728273a4b87d", "fork_of": null, "generation": 5}, "gaps": ["execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["regulatory network. Meanwhile, quantitative real-time PCR (qRT-PCR) was utilized to validate DEcircRNA"], "order_basis": "paper_text_order:1193", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The log-rank test was applied to achieve statistical verification (p < 0.05)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}