Han Fushi, Yang Shusong, Wang Wei, Huang Xinghong, Huang Dongdong, Chen Shuzhen
Department of Nuclear Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China.
Department of Radiotherapy, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China.
Mol Ther Nucleic Acids. 2020 Sep 23;22:981-993. doi: 10.1016/j.omtn.2020.09.020. eCollection 2020 Dec 4.
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 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.
肺腺癌（LUAD）是从不吸烟患者中最主要的肺癌类型。在本研究中，我们鉴定出一种长链非编码RNA（lncRNA）LINC00857，其可能调控LUAD细胞的放射敏感性。使用qRT-PCR和蛋白质免疫印迹分析确定LINC00857和含杆状病毒IAP重复序列5（BIRC5）在LUAD细胞和组织中的表达上调。使用RNA免疫沉淀和染色质免疫沉淀试验验证LINC00857与核因子κB亚基1（NF-κB1）之间的相关性，而通过双荧光素酶报告基因试验确定NF-κB1与BIRC5之间的结合关系。结果表明，LINC00857可在BIRC5启动子区域募集NF-κB1。在LUAD细胞中，响应小干扰LINC00857（si-LINC00857），BIRC5启动子活性受到抑制。沉默LINC00857或BIRC5可降低LUAD细胞的增殖和集落形成，但增强其凋亡和放射敏感性。该实验验证了沉默LINC00857对增强LUAD细胞放射敏感性的作用。我们的结果揭示了LUAD细胞中功能性调控的LINC00857-NF-κB1-BIRC5三联体，提示LINC00857作为LUAD治疗的潜在靶点。
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