非小细胞肺癌组织lncRNA LINC00473表达变化及其临床意义
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摘要
目的探讨非小细胞肺癌(NSCLC)组织长链非编码RNA(lncRNA)LINC00473表达变化及其临床意义。方法选择NSCLC组织及其配对的癌旁正常组织各58例份,采用RT-qPCR法检测lncRNA LINC00473表达。以NSCLC组织lncRNA LINC00473相对表达量的中位数为界,将患者分为lncRNA LINC00473高表达者与低表达者,比较不同lncRNA LINC00473表达者术后生存时间。取传3代、对数生长期、生长状态良好的肺癌A549细胞,随机分为si-LINC00473组、si-Scramble组,分别转染si-LINC00473、si-Scramble。收集两组转染48 h细胞,采用RT-qPCR法检测lncRNA LINC00473表达;分别采用CCK-8法、AnnexinV-FITC/PI双染法、Transwell迁移实验检测细胞增殖、凋亡和迁移能力。结果 NSCLC组织与癌旁正常组织lncRNA LINC00473相对表达量分别为1.89±0.132、1.16±0.076,二者比较P<0.05。lncRNA LINC00473高表达者36例、低表达者22例,二者术后生存时间分别为(26.77±5.82)、(41.96±8.75)个月,二者比较P<0.05。si-LINC00473组、si-Scramble组lncRNA LINC00473相对表达量分别为0.26±0.07、1.14±0.15,两组比较P<0.05。与si-Scramble组比较,si-LINC00473组细胞增殖和迁移能力均明显降低,细胞凋亡率明显升高(P均<0.05)。结论 NSCLC组织lncRNA LINC00473高表达;敲低lncRNA LINC00473表达,可抑制NSCLC细胞增殖和迁移能力并能促进其凋亡。lncRNA LINC00473有可能成为NSCLC基因治疗的潜在靶点。
Objective To investigate the expression of long non-coding RNA(lncRNA) LINC00473 in non-small-cell lung cancer(NSCLC) and to evaluate its association with clinical indexes. Methods Fifty-eight NSCLC tissues and their matched normal tissues were collected. The expression of lncRNA LINC00473 was detected by RT-qPCR. Based on the median of the relative expression of lncRNA LINC00473 in NSCLC tissues, patients were divided into the high and low expression groups. The survival time of patients with different expression of lncRNA LINC00473 was compared. A549 cells of the third generation, in the logarithmic growth and with good growth status were randomly divided into the si-LINC00473 group and si-Scramble group, which were transfected with si-LINC00473 and si-Scramble, respectively. After 48 hours of transfection, the expression of lncRNA LINC00473 was detected by RT-qPCR, and the proliferation, apoptosis and migration of the cells were detected by CCK-8, AnnexinV-FITC/PI staining, and Transwell migration assay, respectively. Results The relative expression levels of lncRNA LINC00473 in the normal tissues and NSCLC tissues were 1.16±0.076 and 1.89±0.132, respectively(both P<0.05). There were 36 cases with high expression of lncRNA LINC00473 and 22 cases with low expression. The survival time after operation was 26.77±5.82 and 41.96±8.75 months, respectively(P<0.05). The relative expression levels of lncRNA LINC00473 in the si-LINC00473 group and si-Scramble group were 0.26±0.07 and 1.14±0.15, respectively. Compared with the si-Scramble group, the proliferation ability and migration ability decreased significantly, but the apoptotic rate increased in the si-LINC00473 group(all P<0.05). Conclusions The expression of lncRNA LINC00473 is up-regulated in NSCLC tissues. Knocking down the expression of lncRNA LINC00473 can inhibit the proliferation of NSCLC cells, promote apoptosis and inhibit migration. LncRNA LINC00473 may be a potential target for gene therapy of NSCLC.
Objective To investigate the expression of long non-coding RNA(lncRNA) LINC00473 in non-small-cell lung cancer(NSCLC) and to evaluate its association with clinical indexes. Methods Fifty-eight NSCLC tissues and their matched normal tissues were collected. The expression of lncRNA LINC00473 was detected by RT-qPCR. Based on the median of the relative expression of lncRNA LINC00473 in NSCLC tissues, patients were divided into the high and low expression groups. The survival time of patients with different expression of lncRNA LINC00473 was compared. A549 cells of the third generation, in the logarithmic growth and with good growth status were randomly divided into the si-LINC00473 group and si-Scramble group, which were transfected with si-LINC00473 and si-Scramble, respectively. After 48 hours of transfection, the expression of lncRNA LINC00473 was detected by RT-qPCR, and the proliferation, apoptosis and migration of the cells were detected by CCK-8, AnnexinV-FITC/PI staining, and Transwell migration assay, respectively. Results The relative expression levels of lncRNA LINC00473 in the normal tissues and NSCLC tissues were 1.16±0.076 and 1.89±0.132, respectively(both P<0.05). There were 36 cases with high expression of lncRNA LINC00473 and 22 cases with low expression. The survival time after operation was 26.77±5.82 and 41.96±8.75 months, respectively(P<0.05). The relative expression levels of lncRNA LINC00473 in the si-LINC00473 group and si-Scramble group were 0.26±0.07 and 1.14±0.15, respectively. Compared with the si-Scramble group, the proliferation ability and migration ability decreased significantly, but the apoptotic rate increased in the si-LINC00473 group(all P<0.05). Conclusions The expression of lncRNA LINC00473 is up-regulated in NSCLC tissues. Knocking down the expression of lncRNA LINC00473 can inhibit the proliferation of NSCLC cells, promote apoptosis and inhibit migration. LncRNA LINC00473 may be a potential target for gene therapy of NSCLC.
引文
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[13] Bai J,Zhao WY,Li WJ,et al.Long noncoding RNA LINC00473 indicates a poor prognosis of breast cancer and accelerates tumor carcinogenesis by competing endogenous sponging miR-497[J].Eur Rev Med Pharmacol Sci,2019,23(8):3410-3420.
[14] Wang L,Zhang X,Sheng L,et al.LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer[J].Biosci Rep,2018,38(5).pii:BSR20180790.
[15] Han PB,Ji XJ,Zhang M,et al.Upregulation of lncRNA LINC00473 promotes radioresistance of HNSCC cells through activating Wnt/β-catenin signaling pathway[J].Eur Rev Med Pharmacol Sci,2018,22(21):7305-7313.
[16] Chen Z,Li JL,Lin S,et al.cAMP/CREB-regulated LINC00473 marks LKB1-inactivated lung cancer and mediates tumor growth[J].J Clin Invest,2016,126(6):2267-2279.
[17] Chen Z,Lin S,Li JL,et al.CRTC1-MAML2 fusion-induced lncRNA LINC00473 expression maintains the growth and survival of human mucoepidermoid carcinoma cells[J].Oncogene,2018,37(14):1885-1895.
[2] Siegel RL,Miller KD,Jemal A.Cancer statistics,2019[J].CA Cancer J Clin,2019,69(1):7-34.
[3] Martin-Fernandez ML,Clarke DT,Roberts SK,et al.Structure and dynamics of the EGF receptor as revealed by experiments and simulations and its relevance to non-small cell lung cancer[J].Cells,2019,8(4).pii:E316.
[4] Dhanoa JK,Sethi RS,Verma R,et al.Long non-coding RNA:its evolutionary relics and biological implications in mammals:a review[J].J Anim Sci Technol,2018,60:25.
[5] Mai H,Zhou B,Liu L,et al.Molecular pattern of lncRNAs in hepatocellular carcinoma[J].J Exp Clin Cancer Res,2019,38(1):198.
[6] Zhu H,Wang Q,Yao Y,et al.Microarray analysis of long non-coding RNA expression profiles in human gastric cells and tissues with helicobacter pylori infection[J].BMC Med Genomics,2015,8:84.
[7] Shi C,Yang Y,Yu J,et al.The long noncoding RNA LINC00473,a target of microRNA 34a,promotes tumorigenesis by inhibiting ILF2 degradation in cervical cancer[J].Am J Cancer Res,2017,7(11):2157-2168.
[8] 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.
[9] Zhang W,Song Y.LINC00473 predicts poor prognosis and regulates cell migration and invasion in gastric cancer[J].Biomed Pharmacother,2018,107:1-6.
[10] Zhang L,Wang Y,Li X,et al.ZBTB7A enhances osteosarcoma chemoresistance by transcriptionally repressing lncRNA LINC00473-IL24 activity[J].Neoplasia,2017,19(11):908-918.
[11] Sarfi M,Abbastabar M,Khalili E.Long noncoding RNAs biomarker-based cancer assessment[J].J Cell Physiol,2019.doi:10.1002/jcp.28417.[Epub ahead of print]
[12] Mortezaee K,Najafi M,Farhood B,et al.Modulation of apoptosis by melatonin for improving cancer treatment efficiency:an updated review[J].Life Sci,2019,228:228-241.
[13] Bai J,Zhao WY,Li WJ,et al.Long noncoding RNA LINC00473 indicates a poor prognosis of breast cancer and accelerates tumor carcinogenesis by competing endogenous sponging miR-497[J].Eur Rev Med Pharmacol Sci,2019,23(8):3410-3420.
[14] Wang L,Zhang X,Sheng L,et al.LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer[J].Biosci Rep,2018,38(5).pii:BSR20180790.
[15] Han PB,Ji XJ,Zhang M,et al.Upregulation of lncRNA LINC00473 promotes radioresistance of HNSCC cells through activating Wnt/β-catenin signaling pathway[J].Eur Rev Med Pharmacol Sci,2018,22(21):7305-7313.
[16] Chen Z,Li JL,Lin S,et al.cAMP/CREB-regulated LINC00473 marks LKB1-inactivated lung cancer and mediates tumor growth[J].J Clin Invest,2016,126(6):2267-2279.
[17] Chen Z,Lin S,Li JL,et al.CRTC1-MAML2 fusion-induced lncRNA LINC00473 expression maintains the growth and survival of human mucoepidermoid carcinoma cells[J].Oncogene,2018,37(14):1885-1895.