Ricciuti Biagio, Mencaroni Clelia, Paglialunga Luca, Paciullo Francesco, Crinò Lucio, Chiari Rita, Metro Giulio
Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Via Dottori 1, 06156, Perugia, Italy.
Internal Medicine, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Via Dottori 1, 06156, Perugia, Italy.
Med Oncol. 2016 Feb;33(2):18. doi: 10.1007/s12032-016-0731-2. Epub 2016 Jan 19.
Recent advances in tiling array and high throughput analyses revealed that at least 87.3 % of the human genome is actively transcribed, though <3 % of the human genome encodes proteins. This unexpected truth suggests that most of the transcriptome is constituted by noncoding RNA. Among them, high-resolution microarray and massively parallel sequencing analyses identified long noncoding RNAs (lncRNAs) as nonprotein-coding transcripts. lncRNAs are largely polyadenylated and >200 nucleotides in length transcripts, involved in gene expression through epigenetic and transcriptional regulation, splicing, imprinting and subcellular transport. Although lncRNAs functions are largely uncharacterized, accumulating data indicate that they are involved in fundamental biological functions. Conversely, their dysregulation has increasingly been recognized to contribute to the development and progression of several human malignancies, especially lung cancer, which represents the leading cause of cancer-related deaths worldwide. We conducted a comprehensive review of the published literature focusing on lncRNAs function and disruption in nonsmall cell lung cancer biology, also highlighting their value as biomarkers and potential therapeutic targets. lncRNAs are involved in NSCLC pathogenesis, modulating fundamental cellular processes such as proliferation, cell growth, apoptosis, migration, stem cell maintenance and epithelial to mesenchymal transition, also serving as signaling transducers, molecular decoys and scaffolds. Also, lncRNAs represent very promising biomarkers in early-stage NSCLC patients and may become particularly useful in noninvasive screening protocols. lncRNAs may be used as predictive biomarkers for chemotherapy and targeted therapies sensitivity. Furthermore, selectively targeting oncogenic lncRNAs could provide a new therapeutic tool in treating NSCLC patients. lncRNAs disruption plays a pivotal role in NSCLC development and progression. These molecules also serve as diagnostic, prognostic and predictive biomarkers. Characterization of lncRNA genes and their mechanisms of action will enable us to develop a more comprehensive clinical approach, with the final goal to benefit our patients.
基因芯片技术和高通量分析的最新进展表明，尽管人类基因组中只有不到3%的序列编码蛋白质，但至少87.3%的人类基因组处于活跃转录状态。这一意外发现表明，转录组的大部分由非编码RNA构成。其中，高分辨率微阵列和大规模平行测序分析确定长链非编码RNA（lncRNA）为非蛋白质编码转录本。lncRNA大多是聚腺苷酸化的，长度超过200个核苷酸，通过表观遗传和转录调控、剪接、印记和亚细胞运输参与基因表达。虽然lncRNA的功能大多尚未明确，但越来越多的数据表明它们参与了基本的生物学功能。相反，人们越来越认识到它们的失调会促进多种人类恶性肿瘤尤其是肺癌的发生和发展，肺癌是全球癌症相关死亡的主要原因。我们对已发表的文献进行了全面综述，重点关注lncRNA在非小细胞肺癌生物学中的功能和破坏作用，同时强调它们作为生物标志物和潜在治疗靶点的价值。lncRNA参与非小细胞肺癌的发病机制，调节增殖、细胞生长、凋亡、迁移、干细胞维持和上皮-间质转化等基本细胞过程，还可作为信号转导分子、分子诱饵和支架。此外，lncRNA在早期非小细胞肺癌患者中是非常有前景的生物标志物，在无创筛查方案中可能会特别有用。lncRNA可作为化疗和靶向治疗敏感性的预测生物标志物。此外，选择性靶向致癌lncRNA可为治疗非小细胞肺癌患者提供一种新的治疗工具。lncRNA的破坏在非小细胞肺癌的发生和发展中起关键作用。这些分子还可作为诊断、预后和预测生物标志物。对lncRNA基因及其作用机制的表征将使我们能够制定更全面的临床方法，最终目标是使我们的患者受益。
