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YY1 直接抑制 MYCT1,导致喉肿瘤的发生和进展。

YY1 directly suppresses MYCT1 leading to laryngeal tumorigenesis and progress.

机构信息

Department of Medical Genetics, China Medical University, Shenyang, 110122, China.

National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.

出版信息

Cancer Med. 2017 Jun;6(6):1389-1398. doi: 10.1002/cam4.1073. Epub 2017 May 9.

Abstract

YY1 is a key transcription factor and plays different roles in various cancers. However, role and mechanism of YY1 in laryngeal cancer are still unknown. YY1 and MYCT1 mRNA and protein levels were detected by Real-time RT-PCR and Western Blot methods, respectively. Binding of YY1 to MYCT1 promoter was predicted and confirmed by bioinformatics and chromatin immunoprecipitation assays, respectively. MYCT1 promoter activity was assessed by dual luciferase assay system. Laryngeal cancer cell proliferation, migration, and apoptosis were evaluated by cell viability, colony formation, cell scratch assay, transwell assay, and flow cytometry methods, respectively. YY1 and MYCT1 were upregulated and downregulated at transcriptional level in laryngeal cancer, respectively, which showed a negative correlation between YY1 and MYCT1 expression in laryngeal cancer. Significantly higher expression of YY1 and lower expression of MYCT1 were found in laryngeal cancer tissues of patients with lymphatic metastasis than those without metastasis.YY1 directly bound to MYCT1 promoter region and inhibited its promoter activity. YY1 silence had similar biological functions as MYCT1 overexpression in repressiveness of proliferation and migration, and promotion of apoptosis in laryngeal cancer cells. However, the effects of YY1 silence were recovered by MYCT1 knockdown. YY1 promotes proliferation and migration with suppression of apoptosis via directly inhibiting MYCT1 in laryngeal cancer cells, suggesting that YY1 is a useful target as a potential oncogene in laryngeal cancer development and progression.

摘要

YY1 是一种关键的转录因子,在各种癌症中发挥不同的作用。然而,YY1 在喉癌中的作用和机制尚不清楚。我们通过实时 RT-PCR 和 Western blot 方法分别检测了 YY1 和 MYCT1 mRNA 和蛋白水平,通过生物信息学和染色质免疫沉淀实验分别预测和验证了 YY1 与 MYCT1 启动子的结合,通过双荧光素酶报告基因检测系统评估了 MYCT1 启动子活性。通过细胞活力、集落形成、细胞划痕实验、Transwell 实验和流式细胞术分别评估了喉癌细胞的增殖、迁移和凋亡。YY1 和 MYCT1 在喉癌中分别在转录水平上上调和下调,提示 YY1 和 MYCT1 在喉癌中的表达呈负相关。与无转移的患者相比,有淋巴结转移的患者的喉癌组织中 YY1 的表达明显升高,而 MYCT1 的表达明显降低。YY1 直接结合到 MYCT1 启动子区域并抑制其启动子活性。YY1 沉默在抑制喉癌细胞增殖和迁移以及促进凋亡方面具有与 MYCT1 过表达相似的生物学功能。然而,YY1 沉默的作用可以通过 MYCT1 敲低恢复。YY1 通过直接抑制 MYCT1 在喉癌细胞中促进增殖和迁移,同时抑制凋亡,提示 YY1 是一种有用的靶点,作为喉癌发展和进展中潜在的致癌基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a5/5463081/4fa9aa89fe50/CAM4-6-1389-g001.jpg

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