Linc-ROR regulates apoptosis in esophageal squamous cell carcinoma via modulation of p53 ubiquitination by targeting miR-204-5p/MDM2

Han Gao; Tian Wang; Peng ZhangMuhe ShangZhikui GaoFei YangRan Liu

首页> 外文期刊>Journal of cellular physiology. >Linc-ROR regulates apoptosis in esophageal squamous cell carcinoma via modulation of p53 ubiquitination by targeting miR-204-5p/MDM2

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Linc-ROR regulates apoptosis in esophageal squamous cell carcinoma via modulation of p53 ubiquitination by targeting miR-204-5p/MDM2

机译：在食管Linc-ROR调节细胞凋亡鳞状细胞癌p53的通过调制泛素化通过瞄准mir - 204 - 5 - p / MDM2

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The long intergenic noncoding RNA, regulator of reprogramming (linc-ROR) has been reported to participate in tumorigenesis, while its functions and fundamental mechanisms in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, gain-of-function assays showed that linc-ROR upregulation enhanced cell viability, promoted cell proliferation, and inhibited apoptosis. Mechanistically, the regulatory network of linc-ROR/miR-204-5p/MDM2 was established with bioinfor-matics analysis and online databases, then validated via dual-luciferase reporter assays, RNA immunoprecipitation assays in ESCC cells. Linc-ROR positively regulates the expression of MDM2 as a molecular sponge of miR-204-5p. Moreover, results of western blot and coimmunoprecipitation indicated that linc-ROR overexpression enhanced the ubiquitination level of p53, and its downstream apoptosis-related genes have showed higher bcl-2 expression, lower bax, and cleaved caspase-3 expressions, while miR-204-5p could counteract with this effect. Finally, small interfering RNAs tailored to linc-ROR were established to further evaluate its effects on ESCC comprehensively. In summary, this study revealed that linc-ROR modulated cell apoptosis and regulated p53 ubiquitination via targeting miR-204-5p/MDM2 axis, which provides a novel therapeutic insight into treatments for ESCC.

机译：长基因间的非编码RNA,监管机构重组(linc-ROR)已经被报道参与肿瘤发生,而其功能在食管鳞状上皮和基本机制细胞癌(ESCC)尚不清楚。功能研究,化验显示linc-ROR upregulation增强细胞活力,促进细胞增殖和抑制细胞凋亡。网络linc-ROR / mir - 204 - 5 - p / MDM2与bioinfor-matics分析和建立在线数据库,然后验证通过dual-luciferase记者化验,RNA免疫沉淀反应在ESCC细胞化验。Linc-ROR积极调节的表达MDM2的分子海绵mir - 204 - 5 - p。此外,免疫印迹和的结果coimmunoprecipitation表明linc-ROR超表达增强的泛素化水平p53,下游apoptosis-related基因显示更高的bcl - 2表达,低伯灵顿,裂解caspase-3表达式mir - 204 - 5 - p可以抵消这种效应。最后,小干扰rna定制建立了linc-ROR进一步评估对ESCC全面的影响。研究显示,linc-ROR调制单元细胞凋亡和监管p53通过泛素化针对mir - 204 - 5 - p / MDM2轴,它提供了一个小说治疗洞察治疗ESCC。

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来源
《Journal of cellular physiology.》 |2020年第3期|2325-2335|共11页
作者
Han Gao; Tian Wang; Peng ZhangMuhe ShangZhikui GaoFei YangRan Liu;
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作者单位

Department of Occupational and Environmental Health, Key Laboratory of Environmental Medicine;

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正文语种英语
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关键词
online databases; Ubiquitination; Esophageal Squamous Cell CarcinomaApoptosis;

机译：在线数据库,泛素化,食管鳞状细胞CarcinomaApoptosis;

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4. Adu; Aged;; Aged, 80 and over;; Cadherins;; Carcinoma, Squamous Cell;; Cell Nucleus;; Cytoplasm;; Female;; Humans;; Laryngeal Neoplasms;; Male;; Middle Aged;; Neoplasm Staging;; Protein-Serine-Threonine Kinases;; Proto-Oncogene Proteins c-akt;; Retrospective Studies;; beta Catenin;; *成年人;; 老年人;; 老年人, 80以上;; 钙粘着糖蛋白类;; 癌, 鳞状细胞;; 细胞核;; 细胞质;; 喉肿瘤;; 肿瘤分期;; 蛋白质丝氨酸苏氨酸激酶;; 回顾性研究 [J] . Acta Anaesthesiologica Scandinavica . 2009,第10期

机译：Adu; Aged;; Aged, 80 and over;; Cadherins;; Carcinoma, Squamous Cell;; Cell Nucleus;; Cytoplasm;; Female;; Humans;; Laryngeal Neoplasms;; Male;; Middle Aged;; Neoplasm Staging;; Protein-Serine-Threonine Kinases;; Proto-Oncogene Proteins c-akt;; Retrospective Studies;; beta Catenin;; *成年人;; 老年人;; 老年人, 80以上;; 钙粘着糖蛋白类;; 癌, 鳞状细胞;; 细胞核;; 细胞质;; 喉肿瘤;; 肿瘤分期;; 蛋白质丝氨酸苏氨酸激酶;; 回顾性研究
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机译：subamolide B Isolated from medicinal plantCinnamomum subavenium Induces Cytotoxicity in HumanCutaneous squamous Cell Carcinoma Cells throughmitochondrial and CHOp-Dependent Cell Death pathways

Linc-ROR regulates apoptosis in esophageal squamous cell carcinoma via modulation of p53 ubiquitination by targeting miR-204-5p/MDM2

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