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pmid:35476804
Pan-cancer analysis of microRNA expression profiles highlights microRNAs enriched in normal body cells as effective suppressors of multiple tumor types: A study based on TCGA database.
Sharif Moradi · Aryan Kamal · Hamidreza Aboulkheyr Es · Farnoosh Farhadi · Marzieh Ebrahimi · Hamidreza Chitsaz · Ali Sharifi-Zarchi · Hossein Baharvand
PloS one · 2022 doi:10.1371/journal.pone.0267291
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Experiment
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Data
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Analysis
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Complete file
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While antisense oligonucleotides are used to block oncomiRs, delivery of tumour-suppressive miRNAs holds great potential as a potent anti-cancer strategy. Here, we aim to determine, and functionally analyse, miRNAs that are lowly expressed in various types of tumour but abundantly expressed in multiple normal tissues.\nMETHODS: The miRNA sequencing data of 14 cancer types were downloaded from the TCGA dataset. Significant differences in miRNA expression between tumor and normal samples were calculated using limma package (R programming). An adjusted p value < 0.05 was used to compare normal versus tumor miRNA expression profiles. The predicted gene targets were obtained using TargetScan, miRanda, and miRDB and then subjected to gene ontology analysis using Enrichr. Only GO terms with an adjusted p < 0.05 were considered statistically significant. All data from wet-lab experiments (cell viability assays and flow cytometry) were expressed as means ± SEM, and their differences were analyzed using GraphPad Prism software (Student's t test, p < 0.05).\nRESULTS: By compiling all publicly available miRNA profiling data from The Cancer Genome Atlas (TCGA) Pan-Cancer Project, we reveal a small set of tumour-suppressing miRNAs (which we designate as 'normomiRs') that are highly expressed in 14 types of normal tissues but poorly expressed in corresponding tumour tissues. Interestingly, muscle-enriched miRNAs (e.g. miR-133a/b and miR-206) and miRNAs from DLK1-DIO3 locus (e.g. miR-381 and miR-411) constitute a large fraction of the normomiRs. Moreover, we define that the CCCGU motif is absent in the oncomiRs' seed sequences but present in a fraction of tumour-suppressive miRNAs. Finally, the gain of function of candidate normomiRs across several cancer cell types indicates that miR-206 and miR-381 exert the most potent inhibition on multiple cancer types in vitro.\nCONCLUSION: Our results reveal a pan-cancer set of tumour-suppressing miRNAs and highlight the potential of miRNA-replacement therapies for targeting multiple types of tumour.", "claims": [{"id": "claim-method", "statement": "The significant differences in miRNA expression between tumor and normal samples were calculated using limma package with Benjamini-Hochberg correction to determine false discovery rates (FDRs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35476804", "locator": "sections[4] \"Acquisition of TCGA data\" paragraph 2", "quote": "The significant differences in miRNA expression between tumor and normal samples were calculated using limma package with Benjamini-Hochberg correction to determine false discovery rates (FDRs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the paper and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35476804", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the paper and its Supporting Information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified a set of pan-cancer tumor-suppressing miRNAs and found that miR-206 and miR-381 exerted the most potent inhibition across multiple cancer cell types in vitro.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35476804", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "By compiling all publicly available miRNA profiling data from The Cancer Genome Atlas (TCGA) Pan-Cancer Project, we reveal a small set of tumour-suppressing miRNAs (which we designate as ’normomiRs’) that are highly expressed in 14 types of normal tissues but poorly expressed in corresponding tumour tissues."}, {"asset": "source:pmid:35476804", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Finally, the gain of function of candidate normomiRs across several cancer cell types indicates that miR-206 and miR-381 exert the most potent inhibition on multiple cancer types in vitro."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study identified a set of pan-cancer tumor-suppressing miRNAs and found that miR-206 and miR-381 exerted the most potent inhibition across multiple cancer cell types in vitro.", "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:35476804"], "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. 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