Downregulation of long non-coding RNA TUG1 suppresses tumor growth by promoting ubiquitination of MET in diffuse large B-cell lymphoma (Retracted Article)
Downregulation of long non-coding RNA TUG1 suppresses tumor growth by promoting ubiquitination of MET in diffuse large B-cell lymphoma (Retracted Article)
复制标题
长非编码RNA TUG1的下调通过促进弥漫性大B细胞淋巴瘤中MET的泛素化来抑制肿瘤生长
DOI：
10.1007/s11010-019-03588-7
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发表时间：
2019-11-01
影响因子：
4.3
通讯作者：
Xu, Kailin
中科院分区：
文献类型：
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作者：
Cheng, Hai;Yan, Zhiling;Xu, Kailin
长链非编码RNA（lncRNA）可以通过不同的机制调控基因表达，但在弥漫性大B细胞淋巴瘤（DLBCL）中lncRNA与MET蛋白之间的分子机制尚不清楚。采用实时定量PCR和免疫印迹法检测DLBCL组织和细胞系中lncRNA TUG 1和MET的表达。细胞增殖、侵袭和凋亡分别用kit-8法、transwell法和流式细胞仪检测。通过注射携带si-TUG 1的DLBCL细胞建立动物异种移植模型。TUG 1和MET在DLBCL组织和细胞中表达上调。我们证明了MET在TUG 1敲低的DLBCL细胞中发生了改变，并通过RNA下拉和RNA免疫沉淀证实了TUG 1和MET之间的相互作用。此外，TUG 1的敲低通过促进泛素化降低MET蛋白水平，并抑制体外和体内肿瘤生长。我们的研究结果表明，TUG 1通过抑制MET的泛素化和随后的降解发挥其在DLBCL中的致癌功能。通过MET下调TUG 1的敲低抑制DLBCL细胞增殖和肿瘤生长。
Long non-coding RNAs (lncRNAs) can modulate gene expression through different mechanisms, but the fundamental molecular mechanism between lncRNAs and MET protein in diffuse large B-cell lymphoma (DLBCL) was poorly understood. The expression of lncRNA TUG1 and MET in DLBCL tissues and cell lines was determined by quantitative real-time PCR and western blotting. Cell proliferation, invasion and apoptosis were determined by cell counting kit-8 assay, transwell assay and flow cytometer. The animal xenograft model was established by the injection of DLBCL cells carrying si-TUG1. The expression of TUG1 and MET was upregulated in DLBCL tissues and cells. We demonstrated that MET was altered in the TUG1 knockdown DLBCL cells, and confirmed the interaction between TUG1 and MET by RNA pull-down and RNA immunoprecipitation. Furthermore, knockdown of TUG1 reduced MET protein level by promoting ubiquitination, and suppressed tumor growth in vitro and in vivo. Our findings demonstrated that TUG1 exerted its oncogenic function in DLBCL by inhibiting the ubiquitination and the subsequent degradation of MET. Knockdown of TUG1 through MET downregulation suppressed DLBCL cell proliferation and tumor growth.