lncRNA-LINC00473在胃癌组织中的表达及临床意义
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摘要
目的:分析LINC00473在胃癌中的表达情况、临床意义及对人胃癌细胞增殖水平的影响。方法:利用癌症基因组图谱(TCGA)数据库下载胃腺癌相关数据集,分析肿瘤组织与正常组织之间LINC00473的表达差异;利用Kaplan-Meier曲线进行患者生存分析; MTT方法检测胃癌细胞增殖水平、流式细胞术检测凋亡率的改变。结果:与癌旁组织比较,LINC00473在胃癌组织中的表达明显增加,差异具有统计学意义(P <0. 05);生存分析发现,LINC00473表达与胃癌患者OS和DFS时间相关,LINC00473高表达的胃癌患者,OS和DFS时间明显缩短(P <0. 05)。转染LINC00473 si RNA至胃癌细胞后,结果发现与阴性质粒转染组比较:转染si RNA-LINC00473的胃癌细胞,LINC00473表达明显降低; LINC00473表达下调后细胞增殖水平减慢,凋亡率增加。结论:LINC00473是一个新的胃癌生物标记物,可作为潜在的治疗新靶点。
Objective: To investigate the level of lncRNA LINC00473 in gastric cancer and the effect of LINC00473 on cell proliferation. Methods: The data set of gastric adenocarcinoma was downloaded from the cancer genome atlas( TCGA) database,and the differences of LINC00473 expression between tumor tissues and normal tissues were analyzed. The kaplan-meier curve was used for survival analysis. The effects of LINC00473 on gastric cancer cell proliferation and apoptosis was tested using in vitro MTT and flow cytometric assays. Results: lncRNA LINC00473 expression level was significantly increased in gastric cancer tissues in comparison to adjacent non-tumor tissues,and there were statistically differences( P < 0. 05). The survival analysis showed that the expression of LINC00473 in gastric cancer patients had significant effect on the OS and DFS time. Patients with LINC00473 over-expression had shorter OS and DFS time( P < 0. 05). Moreover,knockdown LINC00473 expression in gastric cell line decreased proliferation,enhanced apoptosis compared with transfected negative control. Conclusion: LINC00473 is a novel prognostic biomarker and a potential therapeutic candidate for gastric cancer.
Objective: To investigate the level of lncRNA LINC00473 in gastric cancer and the effect of LINC00473 on cell proliferation. Methods: The data set of gastric adenocarcinoma was downloaded from the cancer genome atlas( TCGA) database,and the differences of LINC00473 expression between tumor tissues and normal tissues were analyzed. The kaplan-meier curve was used for survival analysis. The effects of LINC00473 on gastric cancer cell proliferation and apoptosis was tested using in vitro MTT and flow cytometric assays. Results: lncRNA LINC00473 expression level was significantly increased in gastric cancer tissues in comparison to adjacent non-tumor tissues,and there were statistically differences( P < 0. 05). The survival analysis showed that the expression of LINC00473 in gastric cancer patients had significant effect on the OS and DFS time. Patients with LINC00473 over-expression had shorter OS and DFS time( P < 0. 05). Moreover,knockdown LINC00473 expression in gastric cell line decreased proliferation,enhanced apoptosis compared with transfected negative control. Conclusion: LINC00473 is a novel prognostic biomarker and a potential therapeutic candidate for gastric cancer.
引文
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[15]Zhang L,Wang Y,Li X,et al. ZBTB7A enhances osteosarcoma chemoresistance by transcriptionally repressing lnc RNA LINC00473-IL24 activity[J]. Neoplasia,2017,19(11):908-918.
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[18]Chen H,Yang F,Li X,et al. Long noncoding RNA LNC473 inhibits the ubiquitination of survivin via association with USP9X and enhances cell proliferation and invasion in hepatocellular carcinoma cells[J]. Biochem Biophys Res Commun,2018,499(3):702-710.
[2]Allemani C,Weir HK,Carreira H,et al. Global surveillance of cancer survival 1995-2009:analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries(CONCORD-2)[J]. Lancet,2015,385(9972):977-1010.
[3]Shimada H,Noie T,Ohashi M,et al. Clinical significance of serum tumor markers for gastric cancer:a systematic review of literature by the task force of the Japanese gastric cancer association[J]. Gastric Cancer,2014,17(1):26-33.
[4]Okazaki Y,Furuno M,Kasukawa T,et al. Analysis of the mouse transcriptome based on functional annotation of 60 770 full-length c DNAs[J]. Nature,2002,420(6915):563-573.
[5]Villegas VE,Zaphiropoulos PG. Neighboring gene regulation by antisense long non-coding RNAs[J]. Int J Mol Sci,2015,16(2):3251-3266.
[6]Cipolla GA,de Oliveira JC,Salviano-Silva A,et al. Long noncoding RNAs in multifactorial diseases:Another layer of complexity[J]. Noncoding RNA,2018,4(2):E13.
[7]Hu G,Niu F,Humburg BA,et al. Molecular mechanisms of long noncoding RNAs and their role in disease pathogenesis[J]. Oncotarget,2018,9(26):18648-18663.
[8]Chen LL,Zhao JC. Functional analysis of long noncoding RNAs in development and disease[J]. Adv Exp Med Biol,2014,825(2):129-158.
[9]Li K,Sun D,Gou Q,et al. Long non-coding RNA linc00460 promotes epithelial-mesenchymal transition and cell migration in lung cancer cells[J]. Cancer Lett,2018,420:80-90.
[10]Ding J,Li J,Wang H,et al. Long noncoding RNA CRNDE promotes colorectal cancer cell proliferation via epigenetically silencing DUSP5/CDKN1A expression[J]. Cell Death Dis,2017,8(8):e2997.
[11]Wang Ying,Xin Yan. Hippo signal pathway and related LncRNA in tumors[J]. Modern Oncology,2015,23(21):3190-3193.
[12]Liu Z,Yan Y,Cao SL,et al. Long non-coding RNA SNHG14contributes to gastric cancer development through targeting mi R-145/SOX9 axis[J]. J Cell Biochem,2018. doi:10. 1002/jcb.26889.
[13]Sun W,Yang Y,Xu C,et al. Roles of long noncoding RNAs in gastric cancer and their clinical applications[J]. J Cancer Res Clin Oncol,2016,142(11):2231-2237.
[14]Shi C,Yang Y,Yu J,et al. The long noncoding RNA LINC00473,a target of micro RNA 34a,promotes tumorigenesis by inhibiting ILF2 degradation in cervical cancer[J]. Am J Cancer Res,2017,7(11):2157-2168.
[15]Zhang L,Wang Y,Li X,et al. ZBTB7A enhances osteosarcoma chemoresistance by transcriptionally repressing lnc RNA LINC00473-IL24 activity[J]. Neoplasia,2017,19(11):908-918.
[16]Chen Z,Li JL,Lin S,et al. c AMP/CREB-regulated LINC00473marks LKB1-inactivated lung cancer and mediates tumor growth[J]. J Clin Invest,2016,126(6):2267-2279.
[17]Zhu S,Fu W,Zhang L,et al. LINC00473 antagonizes the tumour suppressor mi R-195 to mediate the pathogenesis of Wilms tumour via IKKα[J]. Cell Prolif,2018. doi:10. 1111/cpr. 12416.
[18]Chen H,Yang F,Li X,et al. Long noncoding RNA LNC473 inhibits the ubiquitination of survivin via association with USP9X and enhances cell proliferation and invasion in hepatocellular carcinoma cells[J]. Biochem Biophys Res Commun,2018,499(3):702-710.