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pmid:26492393
Cancer Specific Long Noncoding RNAs Show Differential Expression Patterns and Competing Endogenous RNA Potential in Hepatocellular Carcinoma.
Jian Zhang · Dahua Fan · Zhixiang Jian · George G Chen · Paul B S Lai
PloS one · 2015 doi:10.1371/journal.pone.0141042
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Experiment
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Complete file
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However, the roles of cancer specific lncRNA and its related competitive endogenous RNAs (ceRNA) network in hepatocellular cell carcinoma (HCC) are not fully understood. The lncRNA profiles in 372 HCC patients, including 372 tumor and 48 adjacent non-tumor liver tissues, from The Cancer Genome Atlas (TCGA) and NCBI GEO omnibus (GSE65485) were analyzed. Cancer specific lncRNAs (or HCC related lncRNAs) were identified and correlated with clinical features. Based on bioinformatics generated from miRcode, starBase, and miRTarBase, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in HCC. We found 177 cancer specific lncRNAs in HCC (fold change ≥ 1.5, P < 0.01), 41 of them were also discriminatively expressed with gender, race, tumor grade, AJCC tumor stage, and AJCC TNM staging system. Six lncRNAs (CECR7, LINC00346, MAPKAPK5-AS1, LOC338651, FLJ90757, and LOC283663) were found to be significantly associated with overall survival (OS, log-rank P < 0.05). 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P < 0.01 and included in GENCODE.", "structure": {"pmcid": "PMC4619599", "section_index": 8, "section_title": "Cancer specific lncRNAs in HCC", "row_count": 29, "column_count": 5}, "table": {"label": "Table 1", "caption": "Twenty eight cancer specific lncRNAs in ceRNA network construction.This table showed 28 cancer specific lncRNAs for ceRNA network construction with absolute fold change ≥ 3.0, P < 0.01 and included in GENCODE.", "rows": [["LncRNA", "Gene ID", "Chromosome", "Expression change (T vs. N)", "Data set"], ["ASMTL-AS1", "ENSG00000236017", "chrX", "Up-regulation", "TCGA"], ["CDKN2B-AS1", "ENSG00000240498", "chr9", "Up-regulation", "TCGA + GEO"], ["CECR7", "ENSG00000237438", "chr22", "Up-regulation", "TCGA"], ["FLVCR1-AS1", "ENSG00000198468", "chr1", "Up-regulation", "TCGA"], ["FOXD2-AS1", "ENSG00000237424", "chr1", "Up-regulation", "TCGA"], ["GAS5", "ENSG00000234741", "chr1", "Up-regulation", "TCGA"], ["IGF2BP2-AS1", "ENSG00000163915", "chr3", "Up-regulation", "TCGA"], ["LINC00152", "ENSG00000222041", "chr2", "Up-regulation", "TCGA"], ["LINC00176", "ENSG00000196421", "chr20", "Up-regulation", "TCGA"], ["LINC00488", "ENSG00000214381", "chr3", "Up-regulation", "TCGA"], ["LINC00685", "ENSG00000226179", "chrX", "Up-regulation", "TCGA"], ["PVT1", "ENSG00000249859", "chr8", "Up-regulation", "TCGA + GEO"], ["RUSC1-AS1", "ENSG00000225855", "chr1", "Up-regulation", "TCGA"], ["SNHG1", "ENSG00000255717", "chr11", "Up-regulation", "TCGA"], ["SNHG3", "ENSG00000242125", "chr1", "Up-regulation", "TCGA + GEO"], ["SNHG4", "ENSG00000281398", "chr5", "Up-regulation", "TCGA + GEO"], ["TSPEAR-AS2", "ENSG00000182912", "chr21", "Up-regulation", "TCGA"], ["ZNF252P-AS1", "ENSG00000255559", "chr8", "Up-regulation", "TCGA"], ["DIO3OS", "ENSG00000258498", "chr14", "Down-regulation", "GEO"], ["FAM99A", "ENSG00000205866", "chr11", "Down-regulation", "TCGA + GEO"], ["FAM99B", "ENSG00000205865", "chr11", "Down-regulation", "TCGA"], ["H19", "ENSG00000130600", "chr11", "Down-regulation", "TCGA"], ["HAND2-AS1", "ENSG00000237125", "chr4", "Down-regulation", "TCGA"], ["HAR1A", "ENSG00000225978", "chr20", "Down-regulation", "TCGA"], ["LINC00238", "ENSG00000196553", "chr14", "Down-regulation", "TCGA"], ["LINC01554", "ENSG00000236882", "chr5", "Down-regulation", "TCGA"], ["PWRN1", "ENSG00000259905", "chr15", "Down-regulation", "GEO"], ["UCA1", "ENSG00000214049", "chr19", "Down-regulation", "TCGA"]], "row_count": 29, "column_count": 5, "numeric_cells": 50, "header_rows": 1, "locator": "section[8]/table-wrap[1]#pone.0141042.t001"}}, {"id": "asset:table:pmid:26492393:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c337b58f5565e801b5e8cd93dfccded0c8e05a64599f3c21820a1bad09cdd0f2", "bytes": 1394, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#pone.0141042.t002", "version": null, "note": "The correlations between cancer specific lncRNAs and clinical features.This table showed 41 cancer specific lncRNA which were also differentially expressed in clinical feature comparisons.", "structure": {"pmcid": "PMC4619599", "section_index": 9, "section_title": "The correlations between cancer specific lncRNAs and clinical features", "row_count": 10, "column_count": 3}, "table": {"label": "Table 2", "caption": "The correlations between cancer specific lncRNAs and clinical features.This table showed 41 cancer specific lncRNA which were also differentially expressed in clinical feature comparisons.", "rows": [["Comparisons", "Down-regulated", "Up-regulated"], ["Gender (Female vs. Male)", "LOC643837, LINC00526, FAM223B, MIR99AHG, LINC01554, TTTY15", "H19, LINC00092, MIR600HG, LOC645676, COLCA1, LOC723809"], ["Race (White vs. Asian)", "GAS5, SNHG7, LOC100128191, SNHG1, HCG18", "HCG11, LINC00242, GLIDR, LINC00261, LINC00638, LINC00574"], ["Tumor grade (G3 + G4 vs. G1 + G2)", "LOC255167, FAM99A, LINC00574, LOC399959, A1BG-AS1, LINC00526, LINC00261, MIR22HG, LOC643837", "MALAT1, SNHG12, HCG18, SNHG20, ZFAS1, LOC440944, SNHG7, LOC100128191, MCM3AP-AS1, SNHG1, KCNQ1OT1, DSCR9, GAS5, LOC92659"], ["AJCC TNM staging system (T3 + T4 vs. T1 + T2)", "LOC255167, LINC01554, LINC01558, A1BG-AS1", "MCM3AP-AS1"], ["AJCC pathological stage (III + IV vs. I + II)", "LOC255167, LINC01554, LINC01558, A1BG-AS1", "UCA1"], ["Vascular invasion (No vs. Yes)", "MAPKAPK5-AS1, HNF1A-AS1, DSCR9", "FAM99A"], ["New tumor event (Yes vs. No)", "MIR22HG", ""], ["Tumor status (With tumor vs. Tumor free)", "MIR22HG", ""], ["Age at diagnosis (≥ 61 vs. < 61)", "", "LINC01554, LINC00526, LOC255167"]], "row_count": 10, "column_count": 3, "numeric_cells": 13, "header_rows": 1, "locator": "section[9]/table-wrap[1]#pone.0141042.t002"}}, {"id": "asset:table:pmid:26492393:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7097a7f0cc6780f3226e983e4739144683a9961af609b7ceb7d47e4754130c67", "bytes": 952, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#pone.0141042.t003", "version": null, "note": "Putative miRNAs that may target cancer specific lncRNAs by MREs.miR-199A-1 and miR-199A-2 were regards as a single miRNA in our study", "structure": {"pmcid": "PMC4619599", "section_index": 10, "section_title": "miRNA targeting lncRNAs predicted by miRcode and starBase", "row_count": 16, "column_count": 2}, "table": {"label": "Table 3", "caption": "Putative miRNAs that may target cancer specific lncRNAs by MREs.miR-199A-1 and miR-199A-2 were regards as a single miRNA in our study", "rows": [["lncRNA", "miRNAs"], ["LINC00176", "miR-424, miR-184, miR-214, miR-93"], ["PVT1", "miR-195, miR-424, miR-183, miR-199A-1/2, miR-214, miR-383, miR-93"], ["LINC00488", "miR-139"], ["RUSC1-AS1", "miR-10B, miR-135A-1, miR-139, miR-182, miR-199A-1/2, miR-214, miR-96"], ["FLVCR1-AS1", "miR-375"], ["GAS5", "miR-10B, miR-139, miR-182, miR-490, miR-93, miR-96"], ["UCA1", "miR-214, miR-383"], ["SNHG1", "miR-182, miR-195, miR-383, miR-424"], ["SNHG3", "miR-135A-1, miR-139, miR-182"], ["CDKN2B-AS1", "miR-10B"], ["LINC00152", "miR-376C"], ["CECR7", "miR-199A-1/2, miR-214"], ["DIO3OS", "miR-10B, miR-139, miR-199A-1/2, miR-214, miR-34C"], ["H19", "miR-93"], ["LINC00238", "miR-33B, miR-375"]], "row_count": 16, "column_count": 2, "numeric_cells": 20, "header_rows": 1, "locator": "section[10]/table-wrap[1]#pone.0141042.t003"}}, {"id": "asset:table:pmid:26492393:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:5609bef77b85e8006513772958f7dcebda860db19d4377260fe69b19253a69f9", "bytes": 1829, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#pone.0141042.t004", "version": null, "note": "Validation of miRNA targets.", "structure": {"pmcid": "PMC4619599", "section_index": 11, "section_title": "miRNA targets predicted by miRTarBase", "row_count": 18, "column_count": 2}, "table": {"label": "Table 4", "caption": "Validation of miRNA targets.", "rows": [["miRNA", "mRNAs targeted by miRNAs"], ["miR-10B", "PPARA, NF1, CDKN2A, HOXD10, KLF4, NCOR2, CDKN1A, TFAP2C, BCL2L11"], ["miR-135A-1", "JAK2, NR3C2, APC, MYC"], ["miR-139", "FOS"], ["miR-182", "CDKN1A, FOXO1, MITF, FOXO3, RARG, ADCY6, CLOCK, TSC22D3, CYLD, BCL2, CCND2, PDCD4, RECK, EP300, FGF9, NTM"], ["miR-183", "SRSF2, PDCD4, AKAP12, FOXO1, ITGB1, KIF2A, BTRC, EZR, IDH2"], ["miR-184", "AKT2, INPPL1, NFATC2"], ["miR-195", "WEE1, E2F3, CDK6, BCL2, CCND1, RUNX2, RAF1, CCL4, BCL2L11, MECP2, CCND3, TBCCD1, VEGFA, SKI, KRT7, SLC2A3, CAB39, BCL2L2"], ["miR-199A-1/2", "CD44, IKBKB, MET, HIF1A, SMARCA2, SMARCA2, MAPK1, DDR1, MAP3K11, FUT4, CAV2, EZH2, CCNL1, MAPK9, AKT1, MAPK8, MAPK14, LIF, JUNB, MED6, MECP2, ETS2, EDN1, TMEM54, SIRT1"], ["miR-214", "PTEN, MAP2K3, MAPK8, PLXNB1, EZH2, POU4F2, GALNT7, XBP1, DAPK1, SRGAP1, TWIST1, BCL2L2, ING4, FLOT1, MAP2K5, HSPD1, AHSA1, CPNE7, RASA1, YWHAQ, ARL2, AP3B1"], ["miR-33B", "BCL2, ABCA1"], ["miR-34C", "MET, CDK4, NOTCH1, BCL2, E2F3, MYB, CAV1, CCNE2, MYCN, NOTCH4, ULBP2, MYC, SRSF2, SOX2, NANOG"], ["miR-375", "ELAVL4, YWHAZ, TIMM8A, PDK1, YAP1, MTDH, RASD1, YY1AP1, RHOA, KCNQ2, MTPN, USP1, JAK2, C1QBP, PLAG1, BCL2L11, RAB10, PARP1, CAB39, DLG4, ITGB1, SETD8, CASP3, CDC42, EIF2AK2, BCL2, NCAM1, LEPROTL1"], ["miR-376C", "ACVR1C, IGF1R"], ["miR-383", "DIO1, IRF1, VEGFA"], ["miR-424", "HIF1A, CUL2, SPI1, PLAG1, CCNE1, CCND3, CDK6, CCND1, MAP2K1, WEE1, NFIA, LGALS3, MYB, SIAH1, CCNF, CDC14A, CDC25A, CHEK1, KIF23, ATF6, ANLN, FGFR1, PIAS1, ITPR1"], ["miR-93", "CDKN1A, E2F1, ITGB8, TUSC2, TP53INP1, KAT2B, PTEN, LATS2, MAPK9, VEGFA"], ["miR-96", "CDKN1A, KRAS, FOXO1, FOXO3, ADCY6, REV1, RAD51, MITF, HTR1B, PRMT5"]], "row_count": 18, "column_count": 2, "numeric_cells": 26, "header_rows": 1, "locator": "section[11]/table-wrap[1]#pone.0141042.t004"}}, {"id": "asset:table:pmid:26492393:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:28d168fcd752bbad079ce473bddfd753ca780dce429f52f5b2bef77fbc054513", "bytes": 900, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#pone.0141042.t005", "version": null, "note": "Top 15 KEEG pathways enriched by the coding genes involved in ceRNA network (P < 0.0001).The P value was corrected for multiple hypothesis testing using the Benjamini-Hochberg method (Please also refer to S3 Table)", "structure": {"pmcid": "PMC4619599", "section_index": 12, "section_title": "ceRNA network construction and KEEG pathway analysis", "row_count": 18, "column_count": 3}, "table": {"label": "Table 5", "caption": "Top 15 KEEG pathways enriched by the coding genes involved in ceRNA network (P < 0.0001).The P value was corrected for multiple hypothesis testing using the Benjamini-Hochberg method (Please also refer to S3 Table)", "rows": [["", "KEEG pathways", "No. of Genes"], ["Cancer related", "", ""], ["", "Pathways in cancer", "41"], ["Pancreatic cancer", "19"], ["Melanoma", "19"], ["Prostate cancer", "19"], ["Chronic myeloid leukemia", "16"], ["Colorectal cancer", "16"], ["Glioma", "15"], ["Small cell lung cancer", "15"], ["Bladder cancer", "13"], ["Non-small cell lung cancer", "13"], ["Non-cancer related", "", ""], ["", "MAPK signaling pathway", "22"], ["Focal adhesion", "21"], ["Cell cycle", "19"], ["Neurotrophin signaling pathway", "18"], ["T cell receptor signaling pathway", "14"]], "row_count": 18, "column_count": 3, "numeric_cells": 15, "header_rows": 1, "locator": "section[12]/table-wrap[1]#pone.0141042.t005"}}], "gaps": ["asset:data:geo:GSE65485 not downloaded", "asset:data:geo:GSE65485 licence not read"]}, "analysis": {"state": 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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": ["GSE65485"], "resolved_accessions": ["GSE65485"], "statements": ["All relevant data are within the paper and its Supporting Information files."], "basis": "The paper names GSE65485 in NCBI GEO and the accession resolves in the repository. 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