Haemmerle Monika, Gutschner Tony
Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Int J Mol Sci. 2015 Jan 8;16(1):1395-405. doi: 10.3390/ijms16011395.
Recent genome-wide expression profiling studies have uncovered a huge amount of novel, long non-protein-coding RNA transcripts (lncRNA). In general, these transcripts possess a low, but tissue-specific expression, and their nucleotide sequences are often poorly conserved. However, several studies showed that lncRNAs can have important roles for normal tissue development and regulate cellular pluripotency as well as differentiation. Moreover, lncRNAs are implicated in the control of multiple molecular pathways leading to gene expression changes and thus, ultimately modulate cell proliferation, migration and apoptosis. Consequently, deregulation of lncRNA expression contributes to carcinogenesis and is associated with human diseases, e.g., neurodegenerative disorders like Alzheimer's Disease. Here, we will focus on some major challenges of lncRNA research, especially loss-of-function studies. We will delineate strategies for lncRNA gene targeting in vivo, and we will briefly discuss important consideration and pitfalls when investigating lncRNA functions in knockout animal models. Finally, we will highlight future opportunities for lncRNAs research by applying the concept of cross-species comparison, which might contribute to novel disease biomarker discovery and might identify lncRNAs as potential therapeutic targets.
最近的全基因组表达谱研究发现了大量新的长链非蛋白质编码RNA转录本（lncRNA）。一般来说，这些转录本表达水平较低，但具有组织特异性，其核苷酸序列通常保守性较差。然而，多项研究表明，lncRNA在正常组织发育中可发挥重要作用，并能调控细胞多能性及分化。此外，lncRNA参与多条导致基因表达变化的分子途径的调控，从而最终调节细胞增殖、迁移和凋亡。因此，lncRNA表达失调会促进肿瘤发生，并与人类疾病相关，如阿尔茨海默病等神经退行性疾病。在此，我们将聚焦lncRNA研究的一些主要挑战，尤其是功能缺失研究。我们将阐述lncRNA基因体内靶向的策略，并简要讨论在敲除动物模型中研究lncRNA功能时的重要注意事项及陷阱。最后，我们将通过应用跨物种比较的概念突出lncRNA研究的未来机遇，这可能有助于发现新的疾病生物标志物，并可能将lncRNA鉴定为潜在的治疗靶点。
