Novel long non-coding RNA LINC02532 promotes gastric cancer cell proliferation, migration, and invasion in vitro
详细信息    查看全文 | 推荐本文 |
  • 英文篇名:Novel long non-coding RNA LINC02532 promotes gastric cancer cell proliferation, migration, and invasion in vitro
  • 作者:Cheng ; Zhang ; Ming-Hui ; Ma ; Yu ; Liang ; Kun-Zhe ; Wu ; Dong-Qiu ; Dai
  • 英文作者:Cheng Zhang;Ming-Hui Ma;Yu Liang;Kun-Zhe Wu;Dong-Qiu Dai;Department of Gastroenterological Surgery, The Fourth Affiliated Hospital of China Medical University;
  • 英文关键词:Gastric cancer;;Long noncoding RNA;;LINC02532;;Prognosis;;Bioinformatics
  • 中文刊名:WJGP
  • 英文刊名:世界胃肠肿瘤学杂志(电子版)(英文版)
  • 机构:Department of Gastroenterological Surgery, The Fourth Affiliated Hospital of China Medical University;
  • 出版日期:2019-02-15
  • 出版单位:World Journal of Gastrointestinal Oncology
  • 年:2019
  • 期:v.11
  • 基金:Supported by National Natural Science Foundation of China,No.30572162;; Natural Science Foundation of Liaoning Province,No.201602817
  • 语种:英文;
  • 页:WJGP201902002
  • 页数:11
  • CN:02
  • 分类号:24-34
摘要
BACKGROUND Long non-coding RNAs(lncRNAs) are a kind of single-stranded RNA of more than 200 nucleotides in length and have no protein-coding function. Amounting studies have indicated that lncRNAs could play a vital role in the initiation and development of cancers, including gastric cancer(GC). Considering the crucial functions of lncRNAs, the identification and exploration of novel lncRNAs in GC is necessary.AIM To explore the role of novel lncRNA LINC02532 in GC.METHODS The upregulated LINC02532 was identified by processing the GC RNA-Seq data from The Cancer Genome Atlas. The qRT-PCR assay was performed to confirm the expression levels in GC cell lines and tissues. Cell proliferation, migration,and invasion were evaluated by the cell counting kit-8, colony formation, wound healing, and Transwell assays. The miRNAs downregulated in GC and sponged by LINC02532 were identified from and predicted by the data from the Firehose and RNA22 software programs, respectively. The miRNA downstream target genes were obtained from the TargetScan, miRDB, and DIANA online tools.Gene functional enrichment analysis was carried out using the Database for Annotation, Visualization, and Integrated Discovery software in the categories of cellular components, biological processes, molecular functions, and KEGG pathways.RESULTS The qRT-PCR assay demonstrated that the LINC02532 expression level was significantly upregulated in the GC cell lines and 52 paired tissues. Kaplan-Meiersurvival analysis based on The Cancer Genome Atlas data showed that patients with higher LINC02532 expression had poorer prognosis than those with lower LINC02532 expression. The correlation analysis between expression and clinicopathological features revealed that high expression of LINC02532 was associated with a high TNM stage(P = 0.008) and poor differentiation grade(P =0.023). Functional experiments showed that LINC02532 promoted GC cell proliferation, migration, and invasion. According to the bioinformatics analysis,LINC02532 may act as a ceRNA by sponging downregulated miR-129-5 p and miR-490-5 p. Target genes of the two miRNAs were selected for further functional enrichment analysis. Importantly, KEGG pathway analysis showed that the genes were mainly involved in transcriptional misregulation in cancer, cell cycle, and TGF-beta, mTOR, and p53 signaling pathways.CONCLUSION The present study suggested that LINC02532 acted as an oncogene in GC and may be a promising target for therapy and prognosis management of GC.
        BACKGROUND Long non-coding RNAs(lncRNAs) are a kind of single-stranded RNA of more than 200 nucleotides in length and have no protein-coding function. Amounting studies have indicated that lncRNAs could play a vital role in the initiation and development of cancers, including gastric cancer(GC). Considering the crucial functions of lncRNAs, the identification and exploration of novel lncRNAs in GC is necessary.AIM To explore the role of novel lncRNA LINC02532 in GC.METHODS The upregulated LINC02532 was identified by processing the GC RNA-Seq data from The Cancer Genome Atlas. The qRT-PCR assay was performed to confirm the expression levels in GC cell lines and tissues. Cell proliferation, migration,and invasion were evaluated by the cell counting kit-8, colony formation, wound healing, and Transwell assays. The miRNAs downregulated in GC and sponged by LINC02532 were identified from and predicted by the data from the Firehose and RNA22 software programs, respectively. The miRNA downstream target genes were obtained from the TargetScan, miRDB, and DIANA online tools.Gene functional enrichment analysis was carried out using the Database for Annotation, Visualization, and Integrated Discovery software in the categories of cellular components, biological processes, molecular functions, and KEGG pathways.RESULTS The qRT-PCR assay demonstrated that the LINC02532 expression level was significantly upregulated in the GC cell lines and 52 paired tissues. Kaplan-Meiersurvival analysis based on The Cancer Genome Atlas data showed that patients with higher LINC02532 expression had poorer prognosis than those with lower LINC02532 expression. The correlation analysis between expression and clinicopathological features revealed that high expression of LINC02532 was associated with a high TNM stage(P = 0.008) and poor differentiation grade(P =0.023). Functional experiments showed that LINC02532 promoted GC cell proliferation, migration, and invasion. According to the bioinformatics analysis,LINC02532 may act as a ceRNA by sponging downregulated miR-129-5 p and miR-490-5 p. Target genes of the two miRNAs were selected for further functional enrichment analysis. Importantly, KEGG pathway analysis showed that the genes were mainly involved in transcriptional misregulation in cancer, cell cycle, and TGF-beta, mTOR, and p53 signaling pathways.CONCLUSION The present study suggested that LINC02532 acted as an oncogene in GC and may be a promising target for therapy and prognosis management of GC.
引文
1 Bray F,Ferlay J,Soerjomataram I,Siegel RL,Torre LA,Jemal A.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin 2018;68:394-424[PMID:30207593 DOI:10.3322/caac.21492]
    2 Suzuki H,Oda I,Abe S,Sekiguchi M,Mori G,Nonaka S,Yoshinaga S,Saito Y.High rate of 5-year survival among patients with early gastric cancer undergoing curative endoscopic submucosal dissection.Gastric Cancer 2016;19:198-205[PMID:25616808 DOI:10.1007/s10120-015-0469-0]
    3 Yu H,Yang AM,Lu XH,Zhou WX,Yao F,Fei GJ,Guo T,Yao LQ,He LP,Wang BM.Magnifying narrow-band imaging endoscopy is superior in diagnosis of early gastric cancer.World J Gastroenterol2015;21:9156-9162[PMID:26290643 DOI:10.3748/wjg.v21.i30.9156]
    4 Kapranov P,Cheng J,Dike S,Nix DA,Duttagupta R,Willingham AT,Stadler PF,Hertel J,Hackermüller J,Hofacker IL,Bell I,Cheung E,Drenkow J,Dumais E,Patel S,Helt G,Ganesh M,Ghosh S,Piccolboni A,Sementchenko V,Tammana H,Gingeras TR.RNA maps reveal new RNA classes and a possible function for pervasive transcription.Science 2007;316:1484-1488[PMID:17510325 DOI:10.1126/science.1138341]
    5 Yan K,Tian J,Shi W,Xia H,Zhu Y.LncRNA SNHG6 is Associated with Poor Prognosis of Gastric Cancer and Promotes Cell Proliferation and EMT through Epigenetically Silencing p27 and Sponging miR-101-3p.Cell Physiol Biochem 2017;42:999-1012[PMID:28683446 DOI:10.1159/000478682]
    6 Li J,Li Z,Zheng W,Li X,Wang Z,Cui Y,Jiang X.LncRNA-ATB:An indispensable cancer-related long noncoding RNA.Cell Prolif 2017;50[PMID:28884871 DOI:10.1111/cpr.12381]
    7 Chen X,Chen Z,Yu S,Nie F,Yan S,Ma P,Chen Q,Wei C,Fu H,Xu T,Ren S,Sun M,Wang Z.Long Noncoding RNA LINC01234 Functions as a Competing Endogenous RNA to Regulate CBFB Expression by Sponging miR-204-5p in Gastric Cancer.Clin Cancer Res 2018;24:2002-2014[PMID:29386218DOI:10.1158/1078-0432.CCR-17-2376]
    8 Karreth FA,Pandolfi PP.ceRNA cross-talk in cancer:when ce-bling rivalries go awry.Cancer Discov2013;3:1113-1121[PMID:24072616 DOI:10.1158/2159-8290.CD-13-0202]
    9 Li D,Yang M,Liao A,Zeng B,Liu D,Yao Y,Hu G,Chen X,Feng Z,Du Y,Zhou Y,He J,Nie Y.Linc00483 as ceRNA regulates proliferation and apoptosis through activating MAPKs in gastric cancer.JCell Mol Med 2018[PMID:29761936 DOI:10.1111/jcmm.13661]
    10 Kong X,Duan Y,Sang Y,Li Y,Zhang H,Liang Y,Liu Y,Zhang N,Yang Q.LncRNA-CDC6 promotes breast cancer progression and function as ceRNA to target CDC6 by sponging microRNA-215.J Cell Physiol 2018[PMID:30362551 DOI:10.1002/jcp.27587]
    11 Wang Z,Jensen MA,Zenklusen JC.A Practical Guide to The Cancer Genome Atlas(TCGA).Methods Mol Biol 2016;1418:111-141[PMID:27008012 DOI:10.1007/978-1-4939-3578-9_6]
    12 Deng M,Br?gelmann J,Kryukov I,Saraiva-Agostinho N,Perner S.FirebrowseR:an R client to the Broad Institute's Firehose Pipeline.Database(Oxford)2017;2017[PMID:28062517 DOI:10.1093/database/baw160]
    13 Miranda KC,Huynh T,Tay Y,Ang YS,Tam WL,Thomson AM,Lim B,Rigoutsos I.A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes.Cell2006;126:1203-1217[PMID:16990141 DOI:10.1016/j.cell.2006.07.031]
    14 Huang da W,Sherman BT,Lempicki RA.Bioinformatics enrichment tools:paths toward the comprehensive functional analysis of large gene lists.Nucleic Acids Res 2009;37:1-13[PMID:19033363DOI:10.1093/nar/gkn923]
    15 Su ZD,Huang Y,Zhang ZY,Zhao YW,Wang D,Chen W,Chou KC,Lin H.iLoc-lncRNA:predict the subcellular location of lncRNAs by incorporating octamer composition into general PseKNC.Bioinformatics 2018;34:4196-4204[PMID:29931187 DOI:10.1093/bioinformatics/bty508]
    16 Agarwal V,Bell GW,Nam JW,Bartel DP.Predicting effective microRNA target sites in mammalian mRNAs.Elife 2015;4[PMID:26267216 DOI:10.7554/eLife.05005]
    17 Wong N,Wang X.miRDB:an online resource for microRNA target prediction and functional annotations.Nucleic Acids Res 2015;43:D146-D152[PMID:25378301 DOI:10.1093/nar/gku1104]
    18 Paraskevopoulou MD,Georgakilas G,Kostoulas N,Vlachos IS,Vergoulis T,Reczko M,Filippidis C,Dalamagas T,Hatzigeorgiou AG.DIANA-microT web server v5.0:service integration into miRNAfunctional analysis workflows.Nucleic Acids Res 2013;41:W169-W173[PMID:23680784 DOI:10.1093/nar/gkt393]
    19 Huang Y,Zhang J,Hou L,Wang G,Liu H,Zhang R,Chen X,Zhu J.LncRNA AK023391 promotes tumorigenesis and invasion of gastric cancer through activation of the PI3K/Akt signaling pathway.J Exp Clin Cancer Res 2017;36:194[PMID:29282102 DOI:10.1186/s13046-017-0666-2]
    20 Sun TT,He J,Liang Q,Ren LL,Yan TT,Yu TC,Tang JY,Bao YJ,Hu Y,Lin Y,Sun D,Chen YX,Hong J,Chen H,Zou W,Fang JY.LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern.Cancer Discov 2016;6:784-801[PMID:27147598 DOI:10.1158/2159-8290.CD-15-0921]
    21 LüMH,Tang B,Zeng S,Hu CJ,Xie R,Wu YY,Wang SM,He FT,Yang SM.Long noncoding RNABC032469,a novel competing endogenous RNA,upregulates hTERT expression by sponging miR-1207-5p and promotes proliferation in gastric cancer.Oncogene 2016;35:3524-3534[PMID:26549025 DOI:10.1038/onc.2015.413]
    22 Moran VA,Perera RJ,Khalil AM.Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs.Nucleic Acids Res 2012;40:6391-6400[PMID:22492512 DOI:10.1093/nar/gks296]
    23 Geisler S,Coller J.RNA in unexpected places:long non-coding RNA functions in diverse cellular contexts.Nat Rev Mol Cell Biol 2013;14:699-712[PMID:24105322 DOI:10.1038/nrm3679]
    24 Liu Q,Jiang J,Fu Y,Liu T,Yu Y,Zhang X.MiR-129-5p functions as a tumor suppressor in gastric cancer progression through targeting ADAM9.Biomed Pharmacother 2018;105:420-427[PMID:29879625 DOI:10.1016/j.biopha.2018.05.105]
    25 Wang Q,Yu J.MiR-129-5p suppresses gastric cancer cell invasion and proliferation by inhibiting COL1A1.Biochem Cell Biol 2018;96:19-25[PMID:28482162 DOI:10.1139/bcb-2016-0254]
    26 Chen D,Wang H,Chen J,Li Z,Li S,Hu Z,Huang S,Zhao Y,He X.MicroRNA-129-5p Regulates Glycolysis and Cell Proliferation by Targeting the Glucose Transporter SLC2A3 in Gastric Cancer Cells.Front Pharmacol 2018;9:502[PMID:29867504 DOI:10.3389/fphar.2018.00502]
    27 Hou DZ,Dai JS,Deng ZB,Yan DG.Overexpression of microRNA-490-5p targeting CDK1 suppresses proliferation and cell cycle progression of gastric cancer cells by inhibiting ERK signaling pathway.Journal of Modern Oncology 2017;25:2565-2572[DOI:10.3969/j.issn.1672-4992.2017.16.010]
    28 Mishra L,Katuri V,Evans S.The role of PRAJA and ELF in TGF-beta signaling and gastric cancer.Cancer Biol Ther 2005;4:694-699[PMID:16096365 DOI:10.4161/cbt.4.7.2015]
    29 Du W,Wang S,Zhou Q,Li X,Chu J,Chang Z,Tao Q,Ng EK,Fang J,Sung JJ,Yu J.ADAMTS9 is a functional tumor suppressor through inhibiting AKT/mTOR pathway and associated with poor survival in gastric cancer.Oncogene 2013;32:3319-3328[PMID:22907434 DOI:10.1038/onc.2012.359]
    30 Du C,Li DQ,Li N,Chen L,Li SS,Yang Y,Hou MX,Xie MJ,Zheng ZD.DDX5 promotes gastric cancer cell proliferation in vitro and in vivo through mTOR signaling pathway.Sci Rep 2017;7:42876[PMID:28216662 DOI:10.1038/srep42876]
    31 Fu H,Wang C,Yang D,Wei Z,Xu J,Hu Z,Zhang Y,Wang W,Yan R,Cai Q.Curcumin regulates proliferation,autophagy,and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling.J Cell Physiol 2018;233:4634-4642[PMID:28926094 DOI:10.1002/jcp.26190]
NGLC 2004-2010.National Geological Library of China All Rights Reserved.
Add:29 Xueyuan Rd,Haidian District,Beijing,PRC. Mail Add: 8324 mailbox 100083
For exchange or info please contact us via email.