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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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Experiment
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Complete file
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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. 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