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Cancer development and therapy resistance: spotlights on the dark side of the genome
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2018-04-10 , DOI: 10.1016/j.pharmthera.2018.04.001
Eleonora Leucci

Cancer research has been focusing so far on genetic alterations in protein-coding genes. However, mounting evidence underlines the importance of epigenetic and post-transcriptional events in cancer progression and therapy resistance. Moreover, recent genome-wide studies show that disease-causing mutations and chromosome rearrangements often span areas of the genome that do not contain any known protein-coding gene. This finding is not surprising, considering that even though the vast majority of the human genome is transcribed, only a minor portion (accounting for less than 2%) encodes for proteins. Among the various classes of transcribed RNAs, long non-coding RNAs are attractive biomarkers and therapeutic targets due to their disease- and stage-restricted expression.

In addition, by taking part in all the major epigenetic and post-transcriptional programs in the cell, long non-coding RNAs are emerging as key regulators of stress responses and therefore they are important non-genetic players in cancer development and progression. Here I discuss the role of lncRNAs in cancer and their promises and pitfalls as biomarkers and therapeutic targets.



中文翻译:

癌症发展和治疗抗性:聚焦于基因组的黑暗面

迄今为止,癌症研究一直集中在蛋白质编码基因的遗传改变上。然而,越来越多的证据强调了表观遗传和转录后事件在癌症进展和治疗耐药性中的重要性。此外,最近的全基因组研究表明,致病突变和染色体重排通常跨越基因组中不包含任何已知蛋白质编码基因的区域。考虑到即使转录了绝大多数人类基因组,也只有一小部分(占不到2%)编码蛋白质,因此这一发现不足为奇。在各种转录的RNA中,长的非编码RNA由于其疾病和阶段受限的表达而成为有吸引力的生物标志物和治疗靶标。

此外,通过参与细胞中所有主要的表观遗传和转录后程序,长的非编码RNA逐渐成为应激反应的关键调节因子,因此它们是癌症发展和进程中的重要非遗传参与者。在这里,我讨论了lncRNA在癌症中的作用及其作为生物标志物和治疗靶点的前景和陷阱。

更新日期:2018-04-10
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