Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong Province, China.
Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
Biochem Pharmacol. 2021 Jun;188:114558. doi: 10.1016/j.bcp.2021.114558. Epub 2021 Apr 21.
Long non-coding RNAs (lncRNAs) are a class of RNA transcripts longer than 200 nucleotides and mostly cannot be translated into proteins. Next-generation transcriptome sequencing of various cell types has enabled the annotation of tens of thousands of lncRNAs in human genome. Varying levels of evidence supports the implications of lncRNAs in the onset and progression of cancers. Ubiquitin is an evolutionarily conserved protein and could post-translationally mark a number of proteins. The most important proteolytic role of ubiquitination is degradation of substrate proteins by the 26S proteasome. Compiling evidences demonstrated that lncRNAs are involved in the accurate execution of protein stability programs via the ubiquitin-proteasome system. In the current review, we systematically summarize the detailed mechanisms how lncRNAs modulate ubiquitination of target proteins, regulate cancerous signaling pathways and control tumorigenesis of gastrointestinal cancers. Although there are still considerable studies on unraveling the complicated interactions between lncRNAs and proteins, we believe that lncRNAs are promising but challenging molecules which may strongly facilitate precision cancer therapeutics in the future.
长链非编码 RNA（lncRNA）是一类长度超过 200 个核苷酸的 RNA 转录本，大多数不能翻译成蛋白质。对各种细胞类型的新一代转录组测序使得能够在人类基因组中注释数以万计的 lncRNA。不同水平的证据支持 lncRNA 在癌症的发生和进展中的作用。泛素是一种进化上保守的蛋白质，可以对许多蛋白质进行翻译后修饰。泛素化最重要的蛋白水解作用是通过 26S 蛋白酶体降解底物蛋白。大量证据表明，lncRNA 通过泛素-蛋白酶体系统参与精确执行蛋白质稳定性程序。在本综述中，我们系统地总结了 lncRNA 调节靶蛋白泛素化、调节癌症信号通路和控制胃肠道癌症发生的详细机制。尽管仍有大量研究用于阐明 lncRNA 与蛋白质之间复杂的相互作用，但我们相信 lncRNA 是很有前途但具有挑战性的分子，它们可能在未来强烈促进精准癌症治疗。
