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长链非编码RNA作为肾细胞癌的致瘤因子和治疗靶点

Long noncoding RNAs as tumorigenic factors and therapeutic targets for renal cell carcinoma.

作者信息

Shen Haiyan, Luo Guomin, Chen Qingjuan

机构信息

Department of Nephrology, 3201 Hospital, Hanzhong, Shaanxi Province, China.

Department of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 40016, China.

出版信息

Cancer Cell Int. 2021 Feb 16;21(1):110. doi: 10.1186/s12935-021-01805-2.

Abstract

Approximately 338,000 patients are diagnosed with kidney cancer worldwide each year, and renal cell carcinoma (RCC), which is derived from renal epithelium, accounts for more than ninety percent of the malignancy. Next generation RNA sequencing has enabled the identification of novel long noncoding RNAs (lncRNAs) in the past 10 years. Recent studies have provided extensive evidence that lncRNAs bind to chromatin modification proteins, transcription factors, RNA-binding proteins and microRNAs, and thereby modulate gene expression through regulating chromatin status, gene transcription, pre-mRNA splicing, mRNA decay and stability, protein translation and stability. In vitro and in vivo studies have demonstrated that over-expression of oncogenic lncRNAs and silencing of tumor suppressive lncRNAs are a common feature of human RCC, and that aberrant lncRNA expression is a marker for poor patient prognosis, and is essential for the initiation and progression of RCC. Because lncRNAs, compared with mRNAs, are expressed in a tissue-specific manner, aberrantly expressed lncRNAs can be better targeted for the treatment of RCC through screening small molecule compounds which block the interaction between lncRNAs and their binding proteins or microRNAs.

摘要

全球每年约有33.8万名患者被诊断出患有肾癌,其中源自肾上皮的肾细胞癌(RCC)占恶性肿瘤的90%以上。在过去十年中,新一代RNA测序技术使得新型长链非编码RNA(lncRNA)得以被识别。最近的研究提供了大量证据表明,lncRNAs可与染色质修饰蛋白、转录因子、RNA结合蛋白和微小RNA结合,从而通过调节染色质状态、基因转录、前体mRNA剪接、mRNA降解和稳定性、蛋白质翻译及稳定性来调控基因表达。体外和体内研究均表明,致癌lncRNAs的过表达以及肿瘤抑制性lncRNAs的沉默是人类RCC的常见特征,而且lncRNA表达异常是患者预后不良的一个标志,并且对RCC的发生和发展至关重要。由于与mRNA相比,lncRNAs以组织特异性方式表达,因此通过筛选可阻断lncRNAs与其结合蛋白或微小RNA之间相互作用的小分子化合物,异常表达的lncRNAs可成为更好的RCC治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e769/7885505/ab6198b7165f/12935_2021_1805_Fig1_HTML.jpg

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