Jiang Ying, Jin Shan, Tan Shisheng, Xue Yingbo, Cao Xue
Department of Oncology, The People's Hospital of Guizhou, No. 83, Zhongshan East Road, Guiyang, 550002, Guizhou, China.
Cancer Cell Int. 2020 Dec 3;20(1):581. doi: 10.1186/s12935-020-01655-4.
Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) exhibits an oncogenic role in multiple cancers, including gastric cancer (GC). But, the functions of NEAT1 in modulating radio-sensitivity of GC and its potential molecular mechanisms have not been totally elucidated.
qRT-PCR was performed to detect the expressions of NEAT1 and microRNA-27b-3p (miR-27b-3p). Kaplan-Meier survival curves for NEAT1 expression in GC created using KM Plotter. Colony formation assay was used to determine the survival fraction. Cell apoptosis was evaluated by flow cytometry. Luciferase reporter assay was used to verify the relationship between miR-27b-3p and NEAT1.
NEAT1 was highly expressed while miR-27b-3p was downregulated in GC tissues and cells. NEAT1 was negatively correlated with that of miR-27b-3p and associated with poor overall survival. Moreover, NEAT1 and miR-27b-3p varied inversely after radiation in GC tissues and cells. Loss of NEAT1 or upregulation of miR-27b-3p increased the effect of radiation on cell survival fraction inhibition and apoptosis promotion. In addition, NEAT1 negatively regulated the expression of miR-27b-3p in GC cells. Interestingly, the depletion of miR-27b-3p dramatically attenuated the NEAT1 knockdown-mediated function in AGS and MKN-45 cells treated with radiation in vitro. Similarly, downregulation of NEAT1 enhanced the radiation-mediated inhibition of tumor growth, which was mitigated by decrease of miR-27b-3p.
NEAT1 depletion enhanced radio-sensitivity of GC by negatively regulating miR-27b-3p in vitro and in vivo.
长链非编码RNA核富集丰富转录本1（NEAT1）在包括胃癌（GC）在内的多种癌症中发挥致癌作用。但是，NEAT1在调节GC放射敏感性中的功能及其潜在分子机制尚未完全阐明。
采用qRT-PCR检测NEAT1和微小RNA-27b-3p（miR-27b-3p）的表达。使用KM Plotter创建GC中NEAT1表达的Kaplan-Meier生存曲线。采用集落形成试验确定存活分数。通过流式细胞术评估细胞凋亡。采用荧光素酶报告基因试验验证miR-27b-3p与NEAT1之间的关系。
NEAT1在GC组织和细胞中高表达，而miR-27b-3p下调。NEAT1与miR-27b-3p呈负相关，并与总体生存率差相关。此外，GC组织和细胞在辐射后NEAT1和miR-27b-3p呈反向变化。NEAT1缺失或miR-27b-3p上调增加了辐射对细胞存活分数抑制和促进凋亡的作用。此外，NEAT1在GC细胞中负调节miR-27b-3p的表达。有趣的是，miR-27b-3p的缺失显著减弱了NEAT1敲低介导的对体外接受辐射的AGS和MKN-45细胞的功能。同样，NEAT1的下调增强了辐射介导的肿瘤生长抑制，而miR-27b-3p的减少则减轻了这种抑制。
在体外和体内，NEAT1缺失通过负调节miR-27b-3p增强了GC的放射敏感性。
