The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USA.
Sci Rep. 2017 Jan 20;7:41008. doi: 10.1038/srep41008.
Spinal cord injury (SCI) remains one of the most debilitating neurological disorders and the majority of SCI patients are in the chronic phase. Previous studies of SCI have usually focused on few genes and pathways at a time. In particular, the biological roles of long non-coding RNAs (lncRNAs) have never been characterized in SCI. Our study is the first to comprehensively investigate alterations in the expression of both coding and long non-coding genes in the sub-chronic and chronic stages of SCI using RNA-Sequencing. Through pathway analysis and network construction, the functions of differentially expressed genes were analyzed systematically. Furthermore, we predicted the potential regulatory function of non-coding transcripts, revealed enriched motifs of transcription factors in the upstream regulatory regions of differentially expressed lncRNAs, and identified differentially expressed lncRNAs homologous to human genomic regions which contain single-nucleotide polymorphisms associated with diseases. Overall, these results revealed critical pathways and networks that exhibit sustained alterations at the sub-chronic and chronic stages of SCI, highlighting the temporal regulation of pathological processes including astrogliosis. This study also provided an unprecedented resource and a new catalogue of lncRNAs potentially involved in the regulation and progression of SCI.
脊髓损伤 (SCI) 仍然是最具致残性的神经疾病之一,大多数 SCI 患者处于慢性期。以前对 SCI 的研究通常一次集中在少数几个基因和途径上。特别是,长非编码 RNA(lncRNA)的生物学作用在 SCI 中从未得到过描述。我们的研究首次使用 RNA 测序全面研究了亚慢性和慢性 SCI 阶段编码和长非编码基因表达的变化。通过通路分析和网络构建,系统地分析了差异表达基因的功能。此外,我们预测了非编码转录物的潜在调控功能,揭示了差异表达 lncRNA 上游调控区转录因子的富集基序,并鉴定了与疾病相关的单核苷酸多态性所在的人类基因组区域的差异表达 lncRNA 同源物。总的来说,这些结果揭示了亚慢性和慢性 SCI 阶段持续变化的关键途径和网络,强调了包括星形胶质细胞增生在内的病理过程的时间调节。这项研究还提供了一个前所未有的资源和一个新的长非编码 RNA 目录,这些 RNA 可能参与 SCI 的调控和进展。