Ragusa Marco, Barbagallo Cristina, Brex Duilia, Caponnetto Angela, Cirnigliaro Matilde, Battaglia Rosalia, Barbagallo Davide, Di Pietro Cinzia, Purrello Michele
BioMolecular, Genome and Complex Systems BioMedicine Unit (BMGS Unit), Section of Biology and Genetics G Sichel, Department of BioMedical Sciences and Biotechnology, University of Catania, Catania, Italy.
IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, Troina, Enna, Italy.
Int J Genomics. 2017;2017:4723193. doi: 10.1155/2017/4723193. Epub 2017 Sep 24.
Over the past few years, noncoding RNAs (ncRNAs) have been extensively studied because of the significant biological roles that they play in regulation of cellular mechanisms. ncRNAs are associated to higher eukaryotes complexity; accordingly, their dysfunction results in pathological phenotypes, including cancer. To date, most research efforts have been mainly focused on how ncRNAs could modulate the expression of protein-coding genes in pathological phenotypes. However, recent evidence has shown the existence of an unexpected interplay among ncRNAs that strongly influences cancer development and progression. ncRNAs can interact with and regulate each other through various molecular mechanisms generating a complex network including different species of RNAs (e.g., mRNAs, miRNAs, lncRNAs, and circRNAs). Such a hidden network of RNA-RNA competitive interactions pervades and modulates the physiological functioning of canonical protein-coding pathways involved in proliferation, differentiation, and metastasis in cancer. Moreover, the pivotal role of ncRNAs as keystones of network structural integrity makes them very attractive and promising targets for innovative RNA-based therapeutics. In this review we will discuss: (1) the current knowledge on complex crosstalk among ncRNAs, with a special focus on cancer; and (2) the main issues and criticisms concerning ncRNAs targeting in therapeutics.
在过去几年中，非编码RNA（ncRNAs）因其在细胞机制调控中发挥的重要生物学作用而受到广泛研究。ncRNAs与高等真核生物的复杂性相关；因此，它们的功能障碍会导致包括癌症在内的病理表型。迄今为止，大多数研究工作主要集中在ncRNAs如何在病理表型中调节蛋白质编码基因的表达。然而，最近的证据表明，ncRNAs之间存在意想不到的相互作用，这对癌症的发展和进展有强烈影响。ncRNAs可以通过各种分子机制相互作用并相互调节，形成一个包括不同种类RNA（如mRNA、miRNA、lncRNA和circRNA）的复杂网络。这种隐藏的RNA-RNA竞争性相互作用网络渗透并调节参与癌症增殖、分化和转移的经典蛋白质编码途径的生理功能。此外，ncRNAs作为网络结构完整性基石的关键作用使其成为基于RNA的创新疗法非常有吸引力和前景的靶点。在本综述中，我们将讨论：（1）关于ncRNAs之间复杂相互作用的当前知识，特别关注癌症；（2）关于ncRNAs在治疗中靶向的主要问题和批评。
