Zhang Ying, Cruickshanks Nichola, Pahuski Mary, Yuan Fang, Dutta Anindya, Schiff David, Purow Benjamin, Abounader Roger
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA
The vast majority of the human genome is transcribed into noncoding RNAs. Among these, microRNAs (miRNA) and long noncoding RNAs (lncRNA) are frequently deregulated in cancer, where they regulate a wide variety of functions. Glioblastoma (GBM) is the most common and the most deadly primary human brain tumor. This chapter reviews the deregulation, functions, mechanisms of action, and clinical applications of miRNAs and lncRNAs in GBM. miRNAs are short noncoding RNAs that broadly and profoundly regulate gene expression. Numerous miRNAs are deregulated in GBM, where their expression levels can serve as diagnostic and prognostic biomarkers. miRNAs can act as oncogenes or tumor suppressors in GBM by regulating the expression of numerous tumor-suppressive or oncogenic proteins. miRNAs regulate all GBM malignancy parameters including tumor cell proliferation, cell survival, invasion, angiogenesis, cancer stem cells, immune escape, and therapy resistance. miRNAs are also secreted in body fluids, where they can be used as biomarkers. Because of their deep involvement in GBM malignancy, efforts are under way to also exploit miRNAs as therapeutic agents or targets. lncRNAs are a diverse group of noncoding RNAs that are >200 nucleotides long. Several lncRNAs are deregulated in GBM, where their expressions can associate with clinical parameters. lncRNAs regulate GBM functions including tumor cell proliferation, survival, invasion, cancer stem cell differentiation, and therapy resistance. lncRNAs exert their actions via transcriptional, post-transcriptional, and epigenetic mechanisms that are only partly understood. Studying noncoding RNAs is important for the understanding, management, and development of future therapies for GBM.
人类基因组的绝大部分被转录为非编码RNA。其中,微小RNA(miRNA)和长链非编码RNA(lncRNA)在癌症中经常发生失调,它们在癌症中调节多种功能。胶质母细胞瘤(GBM)是最常见且最致命的原发性人脑肿瘤。本章综述了miRNA和lncRNA在GBM中的失调、功能、作用机制及临床应用。miRNA是短链非编码RNA,广泛而深刻地调节基因表达。在GBM中,许多miRNA发生失调,其表达水平可作为诊断和预后生物标志物。在GBM中,miRNA可通过调节多种肿瘤抑制蛋白或致癌蛋白的表达,充当癌基因或肿瘤抑制因子。miRNA调节GBM的所有恶性参数,包括肿瘤细胞增殖、细胞存活、侵袭、血管生成、癌症干细胞、免疫逃逸和治疗抗性。miRNA也分泌到体液中,可作为生物标志物。由于它们深度参与GBM的恶性过程,人们也在努力将miRNA开发为治疗药物或靶点。lncRNA是一类多样的非编码RNA,长度超过200个核苷酸。在GBM中,几种lncRNA发生失调,其表达可与临床参数相关。lncRNA调节GBM的功能,包括肿瘤细胞增殖、存活、侵袭、癌症干细胞分化和治疗抗性。lncRNA通过转录、转录后和表观遗传机制发挥作用,而这些机制仅得到部分了解。研究非编码RNA对于理解、管理GBM及开发未来治疗方法具有重要意义。