As a leading cause of cancer deaths worldwide, lung cancer is a collection of diseases with diverse etiologies which can be broadly classified into small-cell lung cancer （SCLC） and non-small-cell lung cancer （NSCL...As a leading cause of cancer deaths worldwide, lung cancer is a collection of diseases with diverse etiologies which can be broadly classified into small-cell lung cancer （SCLC） and non-small-cell lung cancer （NSCLC）. Lung cancer is characterized by genomic and epigenomic alterations; however, mechanisms underlying lung tumorigenesis remain to be elucidated. Long noncoding RNAs （lncRNAs） are a group of non-coding RNAs that consist of ≥ 200 nucleotides but possess low or no protein-coding potential. Accumulating evidence indicates that abnormal expression of lncRNAs is associated with tumorigenesis of various cancers, including lung cancer, through multiple biological mechanisms involving epigenetic, transcriptional, and post-transcriptional alterations. In this review, we highlight the expression and roles of lncRNAs in NSCLC and discuss their potential clinical applications as diagnostic or prognostic biomarkers, as well as therapeutic targets.展开更多
This study aimed to explore Semaphrin4D（Sema4D） expression and clinical significance in non-small cell lung cancer（NSCLC）, and to define the roles and mechanisms of Sema4 D in regulating the malignant behaviors of...This study aimed to explore Semaphrin4D（Sema4D） expression and clinical significance in non-small cell lung cancer（NSCLC）, and to define the roles and mechanisms of Sema4 D in regulating the malignant behaviors of A549 cells by small interfering RNA（siRNA）. Firstly, immunohistochemistry revealed that Sema4 D was more frequently expressed in NSCLC than in lung benign lesion（P〈0.05） and its overexprssion was associated with low differentiation（P〈0.05）, poor pTNM staging（P〈0.05） and occurrence of lymph node（LN） metastasis（P〈0.05）. Endogenous Sema4 D expression was suppressed by Sema4 D siRNA in A549 cells overexpressing Sema4 D. Protein levels of Sema4 D, total Akt and p-Akt were examined by Western blotting. Cell proliferation, migration and invasion abilities were measured by MTT assay and Transwell assay respectively. Results showed that Sema4 D siRNA significantly suppressed phosphorylation of AKT in A549 cells, but it did not alter total AKT expression. In addition, efficient down-regulation of SemaD significantly inhibit cell proliferation（P〈0.05）, migration（P〈0.05） and invasion（P〈0.05） in A549 cells. These findings suggest that Sema4 D might serve as a reliable tool for early prediction of NSCLC poor prognosis. Sema4 D could play an important role in promoting tumor proliferation, migration and metastasis in the NSCLC, by influencing the Akt protein phosphorylation. Inhibition of Sema4 D may be a useful approach for the treatment of NSCLC.展开更多
目的:研究RNA干扰沉默核干细胞因子(nucleostemin,NS)基因表达对人肺腺癌A549细胞株增殖和凋亡的影响。方法:向A549细胞内分别转染靶向NS基因的siRNA表达载体pcDNA4/C-NS-silencer和空载体pcDNA4/C vector作为silencer组和vector组,以...目的:研究RNA干扰沉默核干细胞因子(nucleostemin,NS)基因表达对人肺腺癌A549细胞株增殖和凋亡的影响。方法:向A549细胞内分别转染靶向NS基因的siRNA表达载体pcDNA4/C-NS-silencer和空载体pcDNA4/C vector作为silencer组和vector组,以不转染质粒的A549细胞为normal组,Real-time PCR检测转染pcDNA4/C-NS-silencer对A549细胞内NS基因表达的影响。CCK-8法检测沉默NS基因对A549细胞增殖的影响,流式细胞术检测对细胞周期的影响,Hoechst33258核染色法和流式细胞术检测对细胞凋亡的影响。结果:Silencer组NS基因表达较vector组和normal组明显被抑制(0.166±0.024 vs 0.497±0.022、0.505±0.032,均P<0.01);Silencer组A549细胞增殖活性显著低于vector组和normal组(0.518±0.107 vs 0.855±0.102、0.832±0.158,均P<0.05);Silencer组A549细胞周期阻滞于G0/G1期;Silencer组细胞核皱缩呈致密浓染,染色质碎裂呈块状并有边集现象,且细胞凋亡率较vector组与normal组显著增高[(34.80±6.77)%vs(9.70±1.50)%,(8.16±2.01)%,P<0.01]。结论:RNA干扰沉默NS基因可抑制人肺腺癌A549细胞的增殖,促进细胞凋亡。展开更多
目的运用RNAi技术抑制CD59基因的表达,观察其对非小细胞肺癌细胞株GLC-P增值、凋亡的影响。方法合成可抑制CD59基因的片段,并运用RNA干扰技术,构建重组质粒,通过脂质体转染法将重组质粒转染至非小细胞肺癌细胞株GLC-P,并筛选出稳定表达...目的运用RNAi技术抑制CD59基因的表达,观察其对非小细胞肺癌细胞株GLC-P增值、凋亡的影响。方法合成可抑制CD59基因的片段,并运用RNA干扰技术,构建重组质粒,通过脂质体转染法将重组质粒转染至非小细胞肺癌细胞株GLC-P,并筛选出稳定表达细胞后,采用PCR、MTT、ELISA法检测该稳定表达细胞株的增值、凋亡所受到的影响。结果干扰后的GLC-P细胞株中CD59 m RNA表达量较未干扰组显著降低(P<0.05),同时MTT、ELISA实验检测显示肺癌GLC-P细胞增殖能力降低,可诱导肺癌细胞的凋亡。结论肺癌患者肿瘤细胞中存在CD59高表达,抑制CD59基因表达的同时可抑制GLC-P细胞的增殖能力并诱导细胞凋亡,为非小细胞肺癌的靶向治疗提供了新靶点、新思路。展开更多
基金supported by the National Natural Science Funds for Distinguished Young Scholar(Grant No.81425025)the National Basic Research Program of China(Grant No.2012CB910800)
文摘As a leading cause of cancer deaths worldwide, lung cancer is a collection of diseases with diverse etiologies which can be broadly classified into small-cell lung cancer （SCLC） and non-small-cell lung cancer （NSCLC）. Lung cancer is characterized by genomic and epigenomic alterations; however, mechanisms underlying lung tumorigenesis remain to be elucidated. Long noncoding RNAs （lncRNAs） are a group of non-coding RNAs that consist of ≥ 200 nucleotides but possess low or no protein-coding potential. Accumulating evidence indicates that abnormal expression of lncRNAs is associated with tumorigenesis of various cancers, including lung cancer, through multiple biological mechanisms involving epigenetic, transcriptional, and post-transcriptional alterations. In this review, we highlight the expression and roles of lncRNAs in NSCLC and discuss their potential clinical applications as diagnostic or prognostic biomarkers, as well as therapeutic targets.
基金supported by the National Natural Science Foundation of China(No.30973473)
文摘This study aimed to explore Semaphrin4D（Sema4D） expression and clinical significance in non-small cell lung cancer（NSCLC）, and to define the roles and mechanisms of Sema4 D in regulating the malignant behaviors of A549 cells by small interfering RNA（siRNA）. Firstly, immunohistochemistry revealed that Sema4 D was more frequently expressed in NSCLC than in lung benign lesion（P〈0.05） and its overexprssion was associated with low differentiation（P〈0.05）, poor pTNM staging（P〈0.05） and occurrence of lymph node（LN） metastasis（P〈0.05）. Endogenous Sema4 D expression was suppressed by Sema4 D siRNA in A549 cells overexpressing Sema4 D. Protein levels of Sema4 D, total Akt and p-Akt were examined by Western blotting. Cell proliferation, migration and invasion abilities were measured by MTT assay and Transwell assay respectively. Results showed that Sema4 D siRNA significantly suppressed phosphorylation of AKT in A549 cells, but it did not alter total AKT expression. In addition, efficient down-regulation of SemaD significantly inhibit cell proliferation（P〈0.05）, migration（P〈0.05） and invasion（P〈0.05） in A549 cells. These findings suggest that Sema4 D might serve as a reliable tool for early prediction of NSCLC poor prognosis. Sema4 D could play an important role in promoting tumor proliferation, migration and metastasis in the NSCLC, by influencing the Akt protein phosphorylation. Inhibition of Sema4 D may be a useful approach for the treatment of NSCLC.
文摘目的:研究RNA干扰沉默核干细胞因子(nucleostemin,NS)基因表达对人肺腺癌A549细胞株增殖和凋亡的影响。方法:向A549细胞内分别转染靶向NS基因的siRNA表达载体pcDNA4/C-NS-silencer和空载体pcDNA4/C vector作为silencer组和vector组,以不转染质粒的A549细胞为normal组,Real-time PCR检测转染pcDNA4/C-NS-silencer对A549细胞内NS基因表达的影响。CCK-8法检测沉默NS基因对A549细胞增殖的影响,流式细胞术检测对细胞周期的影响,Hoechst33258核染色法和流式细胞术检测对细胞凋亡的影响。结果:Silencer组NS基因表达较vector组和normal组明显被抑制(0.166±0.024 vs 0.497±0.022、0.505±0.032,均P<0.01);Silencer组A549细胞增殖活性显著低于vector组和normal组(0.518±0.107 vs 0.855±0.102、0.832±0.158,均P<0.05);Silencer组A549细胞周期阻滞于G0/G1期;Silencer组细胞核皱缩呈致密浓染,染色质碎裂呈块状并有边集现象,且细胞凋亡率较vector组与normal组显著增高[(34.80±6.77)%vs(9.70±1.50)%,(8.16±2.01)%,P<0.01]。结论:RNA干扰沉默NS基因可抑制人肺腺癌A549细胞的增殖,促进细胞凋亡。
文摘目的运用RNAi技术抑制CD59基因的表达,观察其对非小细胞肺癌细胞株GLC-P增值、凋亡的影响。方法合成可抑制CD59基因的片段,并运用RNA干扰技术,构建重组质粒,通过脂质体转染法将重组质粒转染至非小细胞肺癌细胞株GLC-P,并筛选出稳定表达细胞后,采用PCR、MTT、ELISA法检测该稳定表达细胞株的增值、凋亡所受到的影响。结果干扰后的GLC-P细胞株中CD59 m RNA表达量较未干扰组显著降低(P<0.05),同时MTT、ELISA实验检测显示肺癌GLC-P细胞增殖能力降低,可诱导肺癌细胞的凋亡。结论肺癌患者肿瘤细胞中存在CD59高表达,抑制CD59基因表达的同时可抑制GLC-P细胞的增殖能力并诱导细胞凋亡,为非小细胞肺癌的靶向治疗提供了新靶点、新思路。
