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STAT1-induced upregulation of lncRNA LINC01123 predicts poor prognosis and promotes the progression of endometrial cancer through miR-516b/KIF4A.
Cell Cycle ( IF 3.4 ) Pub Date : 2020-05-13 , DOI: 10.1080/15384101.2020.1757936
Yuguang Yang 1 , Jin Wu 1 , Hongfeng Zhou 1 , Wenming Liu 1 , Jincai Wang 1 , Qingyuan Zhang 1
Affiliation  

Long non-coding RNAs (lncRNAs) have been proposed as suppressors or promoters in many tumor processes. LncRNA LINC01123 (LINC01123) was a newly identified lncRNA which was firstly functionally analyzed in lung cancer. However, its expression and function in other tumor types were rarely reported. In this study, we firstly confirmed that LINC01123 was highly expressed in both endometrial cancer (EC) tissues and cell lines using bioinformatics analysis and RT-CPR. Then, we preliminarily analyzed the mechanisms involved in overexpression of LINC01123 in EC, finding that STAT1 could bind directly to the LINC01123 promoter region and activate its transcription. Clinical research with 106 patients indicated that high expression of LINC01123 was associated with advanced clinical progression and poor clinical outcome of EC patients. Functionally, knockdown of LINC01123 suppressed the proliferation, migration and invasion of EC cells, and promoted apoptosis. Mechanistically, we observed that LINC01123 may act as an endogenous sponge by competing for miR-516b, thereby regulating KIF4A. Overall, our study revealed a novel LINC01123/miR-516b/KIF4A pathway regulatory axis in EC pathogenesis. LINC01123 may be a novel prognostic biomarker and therapeutic target in EC.Abbreviations: EC: Endometrial cancer; LncRNA: Long non-coding RNA; EMT: epithelial–mesenchymal transition; miRNA: microRNA; qRT-PCR: Quantitative real-time polymerase chain reaction; SPSS: Statistical Package for Social Sciences; Chip: chromatin-immunoprecipitation, TCGA: The Cancer Genome Atlas; CCK-8: Cell Counting Kit-8; KIF4A: Chromosome-associated kinesin KIF4A.



中文翻译:

STAT1 诱导的 lncRNA LINC01123 上调预测不良预后并通过 miR-516b/KIF4A 促进子宫内膜癌的进展。

长链非编码 RNA (lncRNA) 已被提议作为许多肿瘤过程中的抑制因子或启动子。LncRNA LINC01123 (LINC01123) 是一种新发现的 lncRNA,它首先在肺癌中进行了功能分析。然而,很少报道其在其他肿瘤类型中的表达和功能。在这项研究中,我们首先使用生物信息学分析和 RT-CPR 证实 LINC01123 在子宫内膜癌 (EC) 组织和细胞系中均高表达。然后,我们初步分析了 EC 中 LINC01123 过表达的机制,发现 STAT1 可以直接结合 LINC01123 启动子区域并激活其转录。对 106 名患者的临床研究表明,LINC01123 的高表达与 EC 患者的晚期临床进展和不良临床结果相关。在功能上,LINC01123的敲低抑制了EC细胞的增殖、迁移和侵袭,并促进了细胞凋亡。从机制上讲,我们观察到 LINC01123 可能通过竞争 miR-516b 充当内源性海绵,从而调节 KIF4A。总的来说,我们的研究揭示了 EC 发病机制中的一个新的 LINC01123/miR-516b/KIF4A 通路调控轴。LINC01123 可能是 EC 中的新型预后生物标志物和治疗靶点。缩写:EC:子宫内膜癌;lncRNA:长链非编码RNA;EMT:上皮-间质转化;miRNA:微RNA;qRT-PCR:定量实时聚合酶链反应;SPSS:社会科学统计软件包;芯片:染色质免疫沉淀,TCGA:癌症基因组图谱;CCK-8:细胞计数试剂盒-8;KIF4A:染色体相关驱动蛋白 KIF4A。

更新日期:2020-05-13
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