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pmid:29348872

Gene expression profiling reveals U1 snRNA regulates cancer gene expression.

Zhi Cheng · Yu Sun · Xiaoran Niu · Yingchun Shang · Jishou Ruan · Ze Chen · Shan Gao · Tao Zhang

Oncotarget · 2017 doi:10.18632/oncotarget.22842

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Gene expression profiling reveals U1 snRNA regulates cancer gene expression.
doi
10.18632/oncotarget.22842
pmid
29348872
authors array · 8 items
[0]
Zhi Cheng
[1]
Yu Sun
[2]
Xiaoran Niu
[3]
Yingchun Shang
[4]
Jishou Ruan
[5]
Ze Chen
[6]
Shan Gao
[7]
Tao Zhang
journal
Oncotarget
year
2017
abstract
U1 small nuclear RNA (U1 snRNA), as one of the most abundant ncRNAs in human cells, plays an important role in splicing of pre-mRNAs. Compared to previous studies which have focused on the primary function of U1 snRNA and the neurodegenerative diseases caused by abnormalities of U1 snRNA, this study is to investigate how U1 snRNA over-expression affects the expression of mammal genes on a genome-wide scale. By comparing the gene expression profiles of U1 snRNA over-expressed cells with those of their controls using microarray experiments, 916 genes or loci were identified significantly Differentially Expressed (DE). These 595 up-regulated DE genes and 321 down-regulated DE genes were analyzed using annotations from GO categories and pathways from the KEGG database. As a result, three of 12 enriched pathways were well-known cancer pathways, while the other nine pathways were associated to cancers in previous studies. The further analysis of 73 genes involved in 12 pathways suggested that U1 snRNA could regulate cancer gene expression. The microarray data under the GEO Series accession number GSE84304 is available in the NCBI GEO database.
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U1 snRNA over-expression significantly changed the expression of 916 genes or loci in PC-12 cells (595 up-regulated and 321 down-regulated); enrichment was assessed by Gene Set Enrichment Analysis, and the underlying microarray data are available under GEO accession GSE84304.
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By comparing the gene expression profiles of U1 snRNA over-expressed cells with those of their controls using microarray experiments, 916 genes or loci were identified significantly Differentially Expressed (DE). These 595 up-regulated DE genes and 321 down-regulated DE genes were analyzed using annotations from GO categories and pathways from the KEGG database.
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Gene expression profiling reveals cytoplasmic U1 snRNA accumulation may cause cancers
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Complete file
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Compared to previous studies which have focused on the primary function of U1 snRNA and the neurodegenerative diseases caused by abnormalities of U1 snRNA, this study is to investigate how U1 snRNA over-expression affects the expression of mammal genes on a genome-wide scale. By comparing the gene expression profiles of U1 snRNA over-expressed cells with those of their controls using microarray experiments, 916 genes or loci were identified significantly Differentially Expressed (DE). These 595 up-regulated DE genes and 321 down-regulated DE genes were analyzed using annotations from GO categories and pathways from the KEGG database. As a result, three of 12 enriched pathways were well-known cancer pathways, while the other nine pathways were associated to cancers in previous studies. The further analysis of 73 genes involved in 12 pathways suggested that U1 snRNA could regulate cancer gene expression. The microarray data under the GEO Series accession number GSE84304 is available in the NCBI GEO database.", "claims": [{"id": "claim-method", "statement": "The annotations and enrichment analyses by GO terms and KEGG pathways were performed using Gene Set Enrichment Analysis (GSEA) (http://software.broadinstitute.org/gsea/index.jsp).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29348872", "locator": "sections[12] \"Data analysis\" paragraph 2", "quote": "The annotations and enrichment analyses by GO terms and KEGG pathways were performed using Gene Set Enrichment Analysis (GSEA) (http://software.broadinstitute.org/gsea/index.jsp)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data under the GEO Series accession number GSE84304 is available in the NCBI GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29348872", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The microarray data under the GEO Series accession number GSE84304 is available in the NCBI GEO database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "U1 snRNA over-expression significantly changed the expression of 916 genes or loci in PC-12 cells (595 up-regulated and 321 down-regulated); enrichment was assessed by Gene Set Enrichment Analysis, and the underlying microarray data are available under GEO accession GSE84304.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29348872", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "By comparing the gene expression profiles of U1 snRNA over-expressed cells with those of their controls using microarray experiments, 916 genes or loci were identified significantly Differentially Expressed (DE). These 595 up-regulated DE genes and 321 down-regulated DE genes were analyzed using annotations from GO categories and pathways from the KEGG database."}, {"asset": "source:pmid:29348872", "locator": "sections[12] \"Data analysis\" paragraph 2", "quote": "The annotations and enrichment analyses by GO terms and KEGG pathways were performed using Gene Set Enrichment Analysis (GSEA) (http://software.broadinstitute.org/gsea/index.jsp)."}, {"asset": "source:pmid:29348872", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The microarray data under the GEO Series accession number GSE84304 is available in the NCBI GEO database."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "U1 snRNA over-expression significantly changed the expression of 916 genes or loci in PC-12 cells (595 up-regulated and 321 down-regulated); enrichment was assessed by Gene Set Enrichment Analysis, and the underlying microarray data are available under GEO accession GSE84304.", "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:29348872"], "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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1792, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#T1", "version": null, "note": "Enriched pathways induced by U1 snRNA over-expression", "structure": {"pmcid": "PMC5762557", "section_index": 5, "section_title": "Pathway analysis of DE genes", "row_count": 13, "column_count": 3}, "table": {"label": "Table 1", "caption": "Enriched pathways induced by U1 snRNA over-expression", "rows": [["Pathway", "Up-regulated", "Down-regulated"], ["rno04010:MAPK signaling pathway", "Pak1, Nf1, Il1r2, Rras2, Dusp8, Nfkb1, Rapgef2, Fos, Traf2, Dusp5, Myc, Ddit3, Tgfb2, Tnf, Gadd45a, Gadd45g, Dusp1, Gadd45b", "Pla2g2a, Tgfb1, Cd14, Map4k2, Cdc25b, Ntf4, Pla2g6, Fgf2, Ntrk2"], ["rno04110:Cell cycle", "Wee2, Cdkn1a, Smc1b, Mdm2, Cdk6, Cdkn2a, Myc, Tgfb2, Gadd45a, Gadd45g, Gadd45b", "Tgfb1, Rbl2, Cdc6, Cdc25b, Ccne1"], ["rno04060:Cytokine-cytokine receptor interaction", "Il1r2, Tnfsf15, Il9r, Ccl5, Ifnb1, Cxcl2, Tnf, Il22ra2, Csf1, Cx3cl1, Cxcl10, Ltb, Tnfsf18, Il23r, Il6, Ccl4, Cxcl11", "Tnfsf9, Il23a, Csf3"], ["rno04621:NOD-like receptor signaling pathway", "Ripk2, Cxcl1, Nfkb1, Birc3, Ccl5, Tnfaip3, Cxcl2, Tnf, Il6", "Pycard"], ["rno04115:p53 signaling pathway", "Bid, Cdkn1a, Mdm2, Cdk6, Cdkn2a, Gadd45a, Gadd45g, Bbc3, Gadd45b", "Ccne1"], ["rno04623:Cytosolic DNA-sensing pathway", "Nfkb1, Ccl5, Ifnb1, Cxcl10, Il6, Ccl4", "Pycard"], ["rno04622:RIG-I-like receptor signaling pathway", "Ifih1, Nfkb1, Traf2, Ifnb1, Tnf, Dhx58, Isg15, Cxcl10", ""], ["rno04620:Toll-like receptor signaling pathway", "Nfkb1, Fos, Tlr5, Ccl5, Ifnb1, Tnf, Cxcl10, Il6, Cxcl11", "Cd14"], ["rno05220:Chronic myeloid leukemia", "Cdkn1a, Nfkb1, Mdm2, Runx1, Cdk6, Cdkn2a, Myc, Tgfb2", "Tgfb1"], ["rno04640:Hematopoietic cell lineage", "Il1r2, Cd22, Il9r, Tnf, Csf1, Il6", "Cd14, Csf3, Cd37"], ["rno05219:Bladder cancer", "Cdkn1a, Cdh1, Mdm2, Rassf1, Cdkn2a, Myc", ""], ["rno05200:Pathways in cancer", "Bid, Cdkn1a, Cdh1, Nfkb1, Fos, Mdm2, Runx1, Hhip, Traf2, Rassf1, Cdk6, Birc3, Cdkn2a, Myc, Traf1, Tgfb2, Lamc2, Il6", "Tgfb1, Ccne1, Fgf2"]], "row_count": 13, "column_count": 3, "numeric_cells": 25, "header_rows": 1, "locator": "section[5]/table-wrap[1]#T1"}}], "gaps": ["asset:data:geo:GSE84304 not downloaded", "asset:data:geo:GSE84304 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "Gene Set Enrichment Analysis (GSEA)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The annotations and enrichment analyses by GO terms and KEGG pathways were performed using Gene Set Enrichment Analysis (GSEA) (http://software.broadinstitute.org/gsea/index.jsp)."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE84304"], "resolved_accessions": ["GSE84304"], "statements": ["The microarray data under the GEO Series accession number GSE84304 is available in the NCBI GEO database."], "basis": "The paper names GSE84304 in NCBI Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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The microarray data under the GEO Series accession number G", "urther analysis To validate results from the microarray data analysis, the expression levels of six", "which were consistent with results from the microarray data analysis (Figure 3). Pathways in cancer"], "order_basis": "paper_text_order:553", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["in cancer (KEGG: rno05200) were measured by qPCR assays using human cell line (Hela), rat cel", "ession levels of six genes were confirmed by qPCR. Confirmation of microarray results by qPCRT", "(Ccne1, Fgf2 and Tgfb1) were measured using qPCR. (A) Fold changes represent the average expr", "enes (Pcna, Mcm2 and Ki-67) were measured by qPCR assays using human cell line (Hela), rat cel"], "order_basis": "paper_text_order:2692", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["asured by qPCR assays using human cell line (Hela), rat cell line (PC-12) and mouse tissues (t", "Ki-67) by qPCR assays using human cell line (Hela), rat cell line (PC-12) and mouse tissues (t", "When it comes to the experimental results in Hela cells, the Bax/Bcl2 ratio reached 1.003, whi", "i-67 by 10.44, 12.8 and 2.13 fold changes in Hela cells, which suggested that U1 snRNA over-ex"], "order_basis": "paper_text_order:2726", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["t for one week, six 9-week-old C57BL/6J male mice were randomly divided into the treatment group (n", "oup (n=3) and the control group (n=3). These mice were weighed and then anesthetized (0.6 g/kg body", "t was slowly withdrawn. Two month later, six mice were decapitated to obtain their hippocampus tiss", "cell line (Hela), rat cell line (PC-12) and mouse tissues (the hippocampus) from animal experi"], "order_basis": "paper_text_order:2760", "id": "assay:4"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["x genes. (B) Expression levels of three cell-apoptosis marker genes (Bax, Bcl2 and Casp3) and three", "we measured expression levels of three cell-apoptosis marker genes (Bax, Bcl2 and Casp3) and three", "eriments (Supplementary Table 4). Both three apoptosis markers and three proliferation markers were", "t a low Bax/Bcl2 ratio (< 1) is against cell apoptosis, while a high Bax/Bcl2 ratio (>1) is in favo"], "order_basis": "paper_text_order:3964", "id": "assay:5"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["l-proliferation marker genes (Pcna, Mcm2 and Ki-67) were measured by qPCR assays using human ce", "l-proliferation marker genes (Pcna, Mcm2 and Ki-67) by qPCR assays using human cell line (Hela)", "antly increased expression of Pcna, Mcm2 and Ki-67 by 2.95, 4.11 and 1.65 fold changes in PC-12", "antly increased expression of Pcna, Mcm2 and Ki-67 by 10.44, 12.8 and 2.13 fold changes in Hela"], "order_basis": "paper_text_order:4067", "id": "assay:6"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["In-fusion HD Cloning Kit (Clontech, USA) and transfected into E. coli JM109 competent cells (TaKaRa,", "JM109 competent cells (TaKaRa, Japan). After transfection, E. coli cells were being shaken at 150 rpm", "in PC-12 cells. Then, we performed U1 snRNA knockdown experiments using RNAi following the procedu", "io (~ 0.3) in PC-12 cells caused by U1 snRNA knockdown. It is well known that a low Bax/Bcl2 ratio"], "order_basis": "paper_text_order:4759", "id": "assay:7"}]}