Molecular and Cellular Mechanisms of Action of Tumour Suppressor GAS5 LncRNA.
Molecular and Cellular Mechanisms of Action of Tumour Suppressor GAS5 LncRNA.
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DOI：
10.3390/genes6030484
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发表时间：
2015-07-07
期刊：
影响因子：
3.5
通讯作者：
Williams GT
中科院分区：
文献类型：
--
作者：
Pickard MR;Williams GT
人们越来越认识到，lncRNA在基本的生物学过程中发挥着重要的调节作用，因此，它们的调控失调可能会导致包括癌症在内的重大人类疾病。因此，对lncRNA生物学的更好理解可能会为致病机制提供新的见解，从而为诊断和治疗提供新的机会。在这方面特别令人感兴趣的是Gas5 lncRNA，它在多种癌症中下调，表达水平与临床病理特征和患者预后有关。功能研究进一步表明，Gas5 lncRNA既能抑制多种细胞的增殖，又能促进多种细胞的凋亡，这些细胞作用机制可能共同构成其抑瘤作用的基础。与此同时，近年来对Gas5 lncRNA作用的分子机制的理解也取得了进展，包括对某些类固醇激素受体的核转录抑制和miR-21的隔离，影响了细胞生存的关键调控途径。总体而言，这种积累的知识有可能改善癌症的诊断和治疗，并最终改善患者的预后。
It is increasingly recognised that lncRNAs play essential regulatory roles in fundamental biological processes and, consequently, that their dysregulation may contribute to major human diseases, including cancer. Better understanding of lncRNA biology may therefore offer new insights into pathogenetic mechanisms and thereby offer novel opportunities for diagnosis and therapy. Of particular interest in this regard is GAS5 lncRNA, which is down-regulated in multiple cancers, with expression levels related to both clinico-pathological characteristics and patient prognosis. Functional studies have further shown that GAS5 lncRNA both inhibits the proliferation and promotes the apoptosis of multiple cell types, and that together these cellular mechanisms of action are likely to form the basis of its tumour suppressor action. At the same time, advances have been made in our understanding of the molecular mechanisms of GAS5 lncRNA action in recent years, including riborepression of certain steroid hormone receptors and sequestration of miR-21, impacting key regulatory pathways of cell survival. Overall this accumulating knowledge has the potential to improve both the diagnosis and treatment of cancer, and ultimately patient outcome.