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pmid:33639954

Bioinformatic analysis reveals an exosomal miRNA-mRNA network in colorectal cancer.

Jun Ma · Peilong Wang · Lei Huang · Jianxia Qiao · Jianhong Li

BMC medical genomics · 2021 doi:10.1186/s12920-021-00905-2

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2026-11-01T15:41:26Z
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title
Bioinformatic analysis reveals an exosomal miRNA-mRNA network in colorectal cancer.
doi
10.1186/s12920-021-00905-2
pmid
33639954
authors array · 5 items
[0]
Jun Ma
[1]
Peilong Wang
[2]
Lei Huang
[3]
Jianxia Qiao
[4]
Jianhong Li
journal
BMC medical genomics
year
2021
abstract
BACKGROUND: Exosomes play important roles in angiogenesis, drug resistance, and metastasis of colorectal cancer (CRC), but the underlying mechanism has seldom been reported. Herein, our study aimed to reveal an exosomal miRNA-mRNA network involved in CRC by performing bioinformatical analysis. METHODS: The mRNA and miRNA data of colon adenocarcinoma and rectal adenocarcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and exosomal miRNAs data were downloaded from the GEO dataset GSE39833. The differential expression analysis was performed using "limma" and "edgeR". Target mRNAs of miRNAs were predicted using FunRich 3.1.3, miRNAtap and multiMiR. The candidate mRNAs and exosomal miRNAs were obtained by intersecting two groups of differentially expressed miRNAs and intersection of the differential expressed mRNAs and the target mRNAs, respectively. Key mRNAs and exosomal miRNAs were identified by the least absolute shrinkage and selection operator regression analysis, and used to construct the exosomal miRNA-mRNA network. The network verified was by receiver operating characteristic curve, GEPIA and LinkedOmics. Functional enrichment analysis was also performed for studied miRNAs and mRNAs. RESULTS: A total of 6568 differentially expressed mRNAs and 531 differentially expressed miRNAs from TCGA data, and 166 differentially expressed exosomal miRNAs in GSE39833 dataset were identified. Next, 16 key mRNAs and five key exosomal miRNAs were identified from the 5284 candidate mRNAs and 61 candidate exosomal miRNAs, respectively. The exosomal miRNA-mRNA network with high connectivity contained 13 hub mRNAs (CBFB, CDH3, ETV4, FOXQ1, FUT1, GCNT2, GRIN2D, KIAA1549, KRT80, LZTS1, SLC39A10, SPTBN2, and ZSWIM4) and five hub exosomal miRNAs (hsa-miR-126, hsa-miR-139, hsa-miR-141, hsa-miR-29c, and hsa-miR-423). The functional annotation revealed that these hub mRNAs were mainly involved in the regulation of B cell receptor signaling pathway and glycosphingolipid biosynthesis related pathways. All hub mRNAs and hub exosomal miRNAs exhibited high diagnosis value for CRC. Furthermore, the association of the hub mRNAs with overall survival, stages, and MSI phenotype of CRC revealed their important roles in CRC progression. CONCLUSION: This study constructed an exosomal miRNA-mRNA network which may play crucial roles in the carcinogenesis and progression of CRC, thus providing potential diagnostic biomarkers and therapeutic targets for CRC.
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Using R-packages limma and edgeR [21], we performed the DEA with threshold parameters defined as |log2FC| > 1 and FDR < 0.05 (FC: fold change, FDR: false discovery rate) to identify the differentially expressed mRNAs and miRNAs related to both COAD and READ in TCGA database.
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Using R-packages limma and edgeR [21], we performed the DEA with threshold parameters defined as |log2FC| > 1 and FDR < 0.05 (FC: fold change, FDR: false discovery rate) to identify the differentially expressed mRNAs and miRNAs related to both COAD and READ in TCGA database.
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The datasets used and/or analysed during the current study are available from NCBI Gene Expression Omnibus (GEO: GSE39833) https://www.ncbi.nlm.nih.gov/geo/ and the cancer genome database (TCGA: COAD, READ) https://portal.gdc.cancer.gov.
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The datasets used and/or analysed during the current study are available from NCBI Gene Expression Omnibus (GEO: GSE39833) https://www.ncbi.nlm.nih.gov/geo/ and the cancer genome database (TCGA: COAD, READ) https://portal.gdc.cancer.gov.
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[2] object · 4 fields
id
activity-resolve-GSE39833
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE39833
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
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 object · 4 fields
parent_id
pmid:33639954
parent_hash
sha256:91d2dc652d519540b5efdca4b40d58250ebaccb83f93a6cc5595b54cda60c5a8
fork_of
null
gaps array · 6 items
[0]
asset:data:geo:GSE39833 licence not read
[1]
asset:data:geo:GSE39833 not downloaded
[2]
execution.not_run
[3]
review.human_critique
[4]
review.independent_reader
[5]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
differential_expression
definition_version
f2132e96ae6c7a4e
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Using R-packages limma and edgeR [21], we performed the DEA with threshold parameters defined as |log2FC| > 1 and FDR < 0.05 (FC: fold change, FDR: false discovery rate) to identify the differentially expressed mRNAs and miRNAs related to both COAD and READ in TCGA database.
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33639954", "kind": "science-record", "revision": 8, "content_hash": "sha256:c01ec1a2fcef8735a994f01c87068b73213ee9f6203871d77c6ba6a0cf2642a7", "created_at": "2026-11-01T15:41:26Z", "updated_at": "2026-11-01T22:46:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatic analysis reveals an exosomal miRNA-mRNA network in colorectal cancer.", "doi": "10.1186/s12920-021-00905-2", "pmid": "33639954", "authors": ["Jun Ma", "Peilong Wang", "Lei Huang", "Jianxia Qiao", "Jianhong Li"], "journal": "BMC medical genomics", "year": 2021, "abstract": "BACKGROUND: Exosomes play important roles in angiogenesis, drug resistance, and metastasis of colorectal cancer (CRC), but the underlying mechanism has seldom been reported. Herein, our study aimed to reveal an exosomal miRNA-mRNA network involved in CRC by performing bioinformatical analysis.\nMETHODS: The mRNA and miRNA data of colon adenocarcinoma and rectal adenocarcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and exosomal miRNAs data were downloaded from the GEO dataset GSE39833. The differential expression analysis was performed using \"limma\" and \"edgeR\". Target mRNAs of miRNAs were predicted using FunRich 3.1.3, miRNAtap and multiMiR. The candidate mRNAs and exosomal miRNAs were obtained by intersecting two groups of differentially expressed miRNAs and intersection of the differential expressed mRNAs and the target mRNAs, respectively. Key mRNAs and exosomal miRNAs were identified by the least absolute shrinkage and selection operator regression analysis, and used to construct the exosomal miRNA-mRNA network. The network verified was by receiver operating characteristic curve, GEPIA and LinkedOmics. Functional enrichment analysis was also performed for studied miRNAs and mRNAs.\nRESULTS: A total of 6568 differentially expressed mRNAs and 531 differentially expressed miRNAs from TCGA data, and 166 differentially expressed exosomal miRNAs in GSE39833 dataset were identified. Next, 16 key mRNAs and five key exosomal miRNAs were identified from the 5284 candidate mRNAs and 61 candidate exosomal miRNAs, respectively. The exosomal miRNA-mRNA network with high connectivity contained 13 hub mRNAs (CBFB, CDH3, ETV4, FOXQ1, FUT1, GCNT2, GRIN2D, KIAA1549, KRT80, LZTS1, SLC39A10, SPTBN2, and ZSWIM4) and five hub exosomal miRNAs (hsa-miR-126, hsa-miR-139, hsa-miR-141, hsa-miR-29c, and hsa-miR-423). The functional annotation revealed that these hub mRNAs were mainly involved in the regulation of B cell receptor signaling pathway and glycosphingolipid biosynthesis related pathways. All hub mRNAs and hub exosomal miRNAs exhibited high diagnosis value for CRC. Furthermore, the association of the hub mRNAs with overall survival, stages, and MSI phenotype of CRC revealed their important roles in CRC progression.\nCONCLUSION: This study constructed an exosomal miRNA-mRNA network which may play crucial roles in the carcinogenesis and progression of CRC, thus providing potential diagnostic biomarkers and therapeutic targets for CRC.", "claims": [{"id": "claim-method", "statement": "Using R-packages limma and edgeR [21], we performed the DEA with threshold parameters defined as |log2FC| > 1 and FDR < 0.05 (FC: fold change, FDR: false discovery rate) to identify the differentially expressed mRNAs and miRNAs related to both COAD and READ in TCGA database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33639954", "locator": "sections[4] \"Differential expression analysis (DEA)\" paragraph 2", "quote": "Using R-packages limma and edgeR [21], we performed the DEA with threshold parameters defined as |log2FC| > 1 and FDR < 0.05 (FC: fold change, FDR: false discovery rate) to identify the differentially expressed mRNAs and miRNAs related to both COAD and READ in TCGA database."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analysed during the current study are available from NCBI Gene Expression Omnibus (GEO: GSE39833) https://www.ncbi.nlm.nih.gov/geo/ and the cancer genome database (TCGA: COAD, READ) https://portal.gdc.cancer.gov.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33639954", "locator": "sections[24] \"notes\" paragraph 1", "quote": "The datasets used and/or analysed during the current study are available from NCBI Gene Expression Omnibus (GEO: GSE39833) https://www.ncbi.nlm.nih.gov/geo/ and the cancer genome database (TCGA: COAD, READ) https://portal.gdc.cancer.gov."}], "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:33639954"], "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:GSE39833"], "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:GSE39833"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33639954", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12920-021-00905-2", "sha256": "sha256:dae7e9a227b1e80df4d74a884bc8c61accba801e13a1ac71afb24d65e14181ea", "bytes": 38681, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12920-021-00905-2", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7913431", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE39833", "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=GSE39833", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE39833", "version": null, "note": "The datasets used and/or analysed during the current study are available from NCBI Gene Expression Omnibus (GEO: GSE39833) https://www.ncbi.nlm.nih.gov/geo/ and the cancer genome database (TCGA: COAD, READ) https://portal.gdc.cancer.gov.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analysed during the current study are available from NCBI Gene Expression Omnibus (GEO: GSE39833) https://www.ncbi.nlm.nih.gov/geo/ and the cancer genome database (TCGA: COAD, READ) https://portal.gdc.cancer.gov.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM980024", "GSM980025", "GSM980026", "GSM980027", "GSM980028", "GSM980029", "GSM980030", "GSM980031", "GSM980032", "GSM980033", "GSM980034", "GSM980035", "GSM980036", "GSM980037", "GSM980038", "GSM980039", "GSM980040", "GSM980041", "GSM980042", "GSM980043", "GSM980044", "GSM980045", "GSM980046", "GSM980047", "GSM980048", "GSM980049", "GSM980050", "GSM980051", "GSM980052", "GSM980053", "GSM980054", "GSM980055", "GSM980056", "GSM980057", 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exosomes in healthy controls and colorectal cancer patients-1", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33639954:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:933168f3bd1535af7d68214f09c5734cf4534235362554529c9d8ef285f32c7f", "bytes": 814, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#Tab1", "version": null, "note": "Results of differentially expressed mRNAs and miRNAs from TCGA, and exosomal miRNAs of GSE39833", "structure": {"pmcid": "PMC7913431", "section_index": 10, "section_title": "Differential expression analysis of the mRNA and miRNA in COAD and READ", "row_count": 7, "column_count": 9}, "table": {"label": "Table 1", "caption": "Results of differentially 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"sha256:121fd6d19e3efc412559e87e32852b5a79f98255e4b0e3937d190d8ecdaed5b1", "bytes": 1216, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#Tab2", "version": null, "note": "The results of the consistent miRNAs between differentially expressed miRNA and exosomal miRNAs", "structure": {"pmcid": "PMC7913431", "section_index": 11, "section_title": "Screening of candidate mRNAs and exosomal miRNAs", "row_count": 22, "column_count": 3}, "table": {"label": "Table 2", "caption": "The results of the consistent miRNAs between differentially expressed miRNA and exosomal miRNAs", "rows": [["MicroRNA symbol", "MicroRNA symbol", "MicroRNA symbol"], ["hsa-let-7c", "hsa-mir-150", "hsa-mir-337"], ["hsa-let-7d", "hsa-mir-1539", "hsa-mir-362"], ["hsa-mir-100", "hsa-mir-181d", "hsa-mir-421"], ["hsa-mir-106b", "hsa-mir-192", "hsa-mir-423"], ["hsa-mir-10a", "hsa-mir-193b", "hsa-mir-424"], ["hsa-mir-10b", "hsa-mir-197", 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"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": "Using R-packages limma and edgeR [21], we performed the DEA with threshold parameters defined as |log2FC| > 1 and FDR < 0.05 (FC: fold change, FDR: false discovery rate) to identify the differentially expressed mRNAs and miRNAs related to both COAD and READ in TCGA database."}}, {"id": "method-2", "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": 0.7, "band": "medium", "quote": "limma"}}], "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: edger."}, "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": "R1", "reachable": true, "accessions": ["GSE39833"], "resolved_accessions": ["GSE39833"], "statements": ["The datasets used and/or analysed during the current study are available from NCBI Gene Expression Omnibus (GEO: GSE39833) https://www.ncbi.nlm.nih.gov/geo/ and the cancer genome database (TCGA: COAD, READ) https://portal.gdc.cancer.gov."], "basis": "The paper names GSE39833 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:33639954", "data:geo:GSE39833", "asset:table:pmid:33639954:1", "asset:table:pmid:33639954:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE39833"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:27:20Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 28799, "completion_tokens": 1405, "cached_tokens": 528}}, "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:33639954", "type": "paper", "label": "pmid:33639954"}, {"id": "source:pmid:33639954", "type": "manuscript", "label": "PMID 33639954 full text"}, {"id": "data:geo:GSE39833", "type": "dataset", "label": "GEO GSE39833"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33639954", "type": "paper", "label": "pmid:33639954"}, {"id": "source:pmid:33639954", "type": "manuscript", "label": "PMID 33639954 full text"}, {"id": "data:geo:GSE39833", "type": "dataset", "label": "GEO GSE39833"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33639954", "type": "extraction", "used": ["source:pmid:33639954"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE39833", "type": "accession_resolution", "used": ["data:geo:GSE39833"], "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:33639954", "parent_hash": "sha256:91d2dc652d519540b5efdca4b40d58250ebaccb83f93a6cc5595b54cda60c5a8", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE39833 licence not read", "asset:data:geo:GSE39833 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Using R-packages limma and edgeR [21], we performed the DEA with threshold parameters defined as |log2FC| > 1 and FDR < 0.05 (FC: fold change, FDR: false discovery rate) to identify the differentially expressed mRNAs and miRNAs related to both COAD and READ in TCGA database."], "order_basis": "analysis_only", "id": "assay:1"}]}