Silencing of lncRNA LINC00857 Enhances BIRC5-Dependent Radio-Sensitivity of Lung Adenocarcinoma Cells by Recruiting NF-κB1.

Silencing of lncRNA LINC00857 Enhances BIRC5-Dependent Radio-Sensitivity of Lung Adenocarcinoma Cells by Recruiting NF-κB1.
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LNCRNA LINC00857的沉默可通过募集NF-κB1来增强肺腺癌细胞的BIRC5依赖性无线电敏感性。

DOI:
10.1016/j.omtn.2020.09.020
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发表时间:
2020-12-04
期刊:
Molecular therapy. Nucleic acids
影响因子:
--
通讯作者:
Chen S
Chen S
中科院分区:
其他
文献类型:
--
作者:
Han F;Yang S;Wang W;Huang X;Huang D;Chen S

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肺腺癌(LUAD)是从不吸烟患者中的主要肺癌类型。在这项研究中,我们确定了一个长的非编码RNA(lncRNA)LINC 00857,可能调节LUAD细胞的放射敏感性。使用qRT-PCR和蛋白质印迹分析确定LINC 00857和含有IAP重复序列5(BIRC 5)的杆状病毒的表达在LUAD细胞和组织中上调。采用RNA免疫沉淀和染色质免疫沉淀试验验证了LINK 00857与核因子κ B亚基1(NF-κ B 1)之间的相关性,而NF-κ B 1与BIRC 5之间的结合关系则通过双荧光素酶报告基因试验确定。提示LINC 00857可在BIRC 5启动子区募集NF-κB1。BIRC 5启动子活性在LUAD细胞中响应于小干扰LINC 00857(si-LINC 00857)而被抑制。LINC 00857或BIRC 5沉默降低了LUAD细胞的增殖和集落形成,但增强了LUAD细胞的凋亡和放射敏感性。体内实验验证了沉默LINC 00857对LUAD细胞辐射增敏的作用。我们的研究结果揭示了LUAD细胞中的功能调节LINC 00857-NF-κB1-BIRC 5三联体,表明LINC 00857是LUAD治疗的潜在靶点。本研究鉴定了功能调节LINC 00857-NF-κB1-BIRC 5三联体在LUAD细胞放射敏感性中的参与。此外,靶向LINC 00857被强调为在LUAD治疗中降低放射抗性的潜在策略。
Lung adenocarcinoma (LUAD) is a predominant type of lung cancer in never-smoker patients. In this study, we identified a long noncoding RNA (lncRNA) LINC00857 that might regulate radio-sensitivity of LUAD cells. Expression of LINC00857 and baculoviral IAP repeat containing 5 (BIRC5) was determined to be upregulated in LUAD cells and tissues using qRT-PCR and western blot analysis. The correlation between LINC00857 and nuclear factor kappa B subunit 1 (NF-κB1) was verified using RNA immunoprecipitation and chromatin immunoprecipitation assays, while the binding relationship between NF-κB1 and BIRC5 was determined by dual-luciferase reporter assay. It was suggested that LINC00857 could recruit NF-κB1 in BIRC5 promoter region. BIRC5 promoter activity was repressed in response to small interfering-LINC00857 (si-LINC00857) in LUAD cells. Silencing LINC00857 or BIRC5 reduced proliferation and colony formation but enhanced apoptosis and radio-sensitivity of LUAD cells. The experiment in vivo verified the function of silencing LINC00857 on enhancing radio-sensitivity of LUAD cells. Our results reveal a functional regulatory LINC00857-NF-κB1-BIRC5 triplet in LUAD cells, suggesting LINC00857 as a potential target for LUAD treatment. This study identifies the involvement of functional regulatory LINC00857-NF-κB1-BIRC5 triplet in the radio-sensitivity of LUAD cells. Furthermore, targeting LINC00857 is highlighted as a potential strategy to reduce radio-resistance in the treatment of LUAD.
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