Yamamoto Hirofumi, Mori Masaki
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita City, Osaka, 565-0871, Japan.
Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Yamadaoka 1-7, Suita City, Osaka, 565-0871, Japan.
Adv Exp Med Biol. 2016;937:239-47. doi: 10.1007/978-3-319-42059-2_13.
The diagnosis and treatment of colorectal cancer (CRC) have improved greatly over recent years; however, CRC is still one of the most common cancers and a major cause of cancer death worldwide. Several recently developed drugs and treatment strategies are currently in clinical trials; however, there is still a compelling need for novel, highly efficacious therapies. MicroRNAs (miRNAs) are short non-coding RNAs consisting of 20-25 nucleotides that regulate post-transcriptional gene expression by binding to the 3'-untranslated region of mRNAs. miRNAs are known to regulate cancer pathways and to be expressed aberrantly in cancer. Since their initial discovery, a large number of miRNAs have been identified as oncogenes, whereas others function as tumor suppressors. Furthermore, signaling pathways that are important in CRC (e.g. the WNT, MAPK, TGF-β, TP53 and PI3K pathways) are regulated by miRNAs. A single miRNA can simultaneously regulate several target genes and pathways, indicating the therapeutic potential of miRNAs in CRC. However, significant obstacles remain to be overcome, such as an efficient miRNA delivery system, and the assessment of safety and side effects. Thus, miRNA therapy is still developing and possesses great potential for the treatment of CRC. In this chapter, we focus on miRNAs related to CRC and summarize previous studies that emphasize the therapeutic aspects of miRNAs in CRC.
近年来,结直肠癌(CRC)的诊断和治疗有了很大改善;然而,CRC仍是全球最常见的癌症之一,也是癌症死亡的主要原因。目前有几种新开发的药物和治疗策略正处于临床试验阶段;然而,仍然迫切需要新型、高效的治疗方法。微小RNA(miRNA)是由20-25个核苷酸组成的短链非编码RNA,通过与mRNA的3'-非翻译区结合来调节转录后基因表达。已知miRNA可调节癌症相关通路,并在癌症中异常表达。自首次发现以来,大量miRNA已被鉴定为癌基因,而其他一些则发挥肿瘤抑制作用。此外,CRC中重要的信号通路(如WNT、MAPK、TGF-β、TP53和PI3K通路)受miRNA调控。单个miRNA可同时调节多个靶基因和通路,这表明miRNA在CRC治疗中具有潜在的治疗价值。然而,仍有一些重大障碍有待克服,如高效的miRNA递送系统,以及安全性和副作用的评估。因此,miRNA治疗仍在发展中,在CRC治疗方面具有巨大潜力。在本章中,我们重点关注与CRC相关的miRNA,并总结以往强调miRNA在CRC治疗方面的研究。