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长链非编码RNA横纹肌肉瘤2相关转录本通过……的泛素化对肺腺癌发挥抗肿瘤作用。 (原文此处不完整)

The long non-coding RNA rhabdomyosarcoma 2-associated transcript exerts anti-tumor effects on lung adenocarcinoma via ubiquitination of .

作者信息

Pei Yaofei, Zhou Bing, Liu Xiqiang

机构信息

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.

Department of Cardiothoracic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

出版信息

Ann Transl Med. 2022 Jan;10(1):10. doi: 10.21037/atm-21-6052.

Abstract

BACKGROUND

Long non-coding RNAs (lncRNAs) play an important role in the post-translational modification of proteins, but the importance of lncRNAs in protein ubiquitination remains unclear. This study investigated to role of the lncRNA rhabdomyosarcoma 2-associated transcript () in lung adenocarcinoma (LUAD).

METHODS

The expression of was analyzed in LUAD samples and normal lung tissues using data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) public databases. Colony formation and transwell assays were used to determine the anti-tumor effects of in human LUAD progression. RNA pull-down assays, RNA immunoprecipitation assays, and mass spectrometry were used to determine the mechanisms by which induces the ubiquitination of SRY-box transcription factor 9 (). Furthermore, animal models were used to determine the effects of on LUAD tumorigenicity .

RESULTS

Compared with normal tissues, expression was significantly downregulated in LUAD samples. This abnormal expression of led to significant changes in the proliferation and migration of LUAD cells both and . The experiments demonstrated that binds directly to the protein, resulting in the ubiquitination of and this was mediated by F-box and WD repeat domain-containing 7 (). Clinically, expression was shown to be positively correlated with the overall survival of LUAD patients.

CONCLUSIONS

These findings revealed that suppressed the signaling pathway to inhibit LUAD growth and metastasis. The -induced ubiquitination of via may be a potential therapeutic target for the treatment of patients with LUAD.

摘要

背景

长链非编码RNA(lncRNAs)在蛋白质的翻译后修饰中发挥重要作用,但lncRNAs在蛋白质泛素化中的重要性仍不清楚。本研究调查了lncRNA横纹肌肉瘤2相关转录本()在肺腺癌(LUAD)中的作用。

方法

利用来自癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)公共数据库的数据,分析LUAD样本和正常肺组织中 的表达。采用集落形成和Transwell实验来确定 在人类LUAD进展中的抗肿瘤作用。采用RNA下拉实验、RNA免疫沉淀实验和质谱分析来确定 诱导SRY盒转录因子9()泛素化的机制。此外,利用动物模型来确定 对LUAD致瘤性的影响。

结果

与正常组织相比,LUAD样本中 的表达显著下调。 的这种异常表达导致LUAD细胞在体外和体内的增殖和迁移发生显著变化。实验表明, 直接与 蛋白结合,导致 的泛素化,这是由含F盒和WD重复结构域7()介导的。临床上, 表达与LUAD患者的总生存期呈正相关。

结论

这些发现揭示了 通过抑制 信号通路来抑制LUAD的生长和转移。 通过 诱导 的泛素化可能是治疗LUAD患者的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e850/8825559/5253563c68a2/atm-10-01-10-f1.jpg

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