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E2F6-Mediated Downregulation of MIR22HG Facilitates the Progression of Laryngocarcinoma by Targeting the miR-5000-3p/FBXW7 Axis.
Molecular and Cellular Biology ( IF 3.2 ) Pub Date : 2020-04-28 , DOI: 10.1128/mcb.00496-19
Hui Chen 1 , Mudunov Ali 2 , Azizyan Ruben 3 , Dimitry Stelmakh 3 , Maksim Pak 3
Affiliation  

Recently, abundant evidence has clarified that long noncoding RNAs (lncRNAs) play an oncogenic or anticancer role in the tumorigenesis and development of diverse human cancers. Described as a crucial regulator in some cancers, MIR22HG has not yet been studied in laryngocarcinoma and therefore the underlying regulatory role of MIR22HG in laryngocarcinoma is worth detecting. In this study, MIR22HG expression in laryngocarcinoma cells was confirmed to be downregulated, and upregulated MIR22HG expression led to suppressive effects on laryngocarcinoma cell proliferation and migration. Molecular mechanism assays revealed that MIR22HG sponges miR-5000-3p in laryngocarcinoma cells. Besides, decreased expression of miR-5000-3p suppressed laryngocarcinoma cell proliferation and migration. Moreover, the FBXW7 gene was reported to be a downstream target gene of miR-5000-3p in laryngocarcinoma cells. More importantly, rescue assays verified that FBXW7 depletion or miR-5000-3p upregulation countervailed the repressive effects of MIR22HG overexpression on laryngocarcinoma progression. In addition, E2F6 was proved to be capable of inhibiting MIR22HG transcription in laryngocarcinoma cells. To sum up, E2F6-induced downregulation of MIR22HG promotes laryngocarcinoma progression through the miR-5000-3p/FBXW7 axis.

中文翻译:

E2F6介导的MIR22HG下调通过靶向miR-5000-3p / FBXW7轴促进喉癌的发展。

最近,大量证据表明,长的非编码RNA(lncRNA)在多种人类癌症的发生和发展中起着致癌或抗癌作用。MIR22HG被描述为某些癌症中的关键调节因子,尚未在喉癌中进行研究,因此值得检测MIR22HG在喉癌中的潜在调节作用。在这项研究中,MIR22HG在喉癌细胞中的表达被证实被下调,而MIR22HG表达的上调导致对喉癌细胞增殖和迁移的抑制作用。分子机理分析表明,MIR22HG使喉癌细胞中的miR-5000-3p海绵化。此外,miR-5000-3p的表达降低抑制了喉癌细胞的增殖和迁移。此外,据报道,FBXW7基因是喉癌细胞中miR-5000-3p的下游靶基因。更重要的是,救援分析证实FBXW7耗竭或miR-5000-3p上调抵消了MIR22HG过度表达对喉癌进展的抑制作用。此外,E2F6被证明能够抑制喉癌细胞中的MIR22HG转录。综上所述,E2F6诱导的MIR22HG下调通过miR-5000-3p / FBXW7轴促进了喉癌的进展。
更新日期:2020-02-24
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