Takata A, Otsuka M, Yoshikawa T, Kishikawa T, Ohno M, Koike K
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan -
Minerva Gastroenterol Dietol. 2013 Jun;59(2):187-203.
MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate gene expression post-transcriptionally through complementary base pairing with thousands of messenger RNAs. Although the target genes and precise biological functions of individual miRNAs remain largely unknown, miRNAs are speculated to play important roles in diverse biological processes in both normal and pathological states. The liver is a vital organ that plays major roles in a number of physiological functions. Recent advances in the study of liver miRNAs using gene-modified mice or in vivo nucleic acid delivery to overexpress specific miRNAs or inhibit miRNA functions have revealed the crucial biological roles of individual miRNAs in physiologically essential liver functions in vivo. Because miRNA-based strategies are being applied to clinical therapeutics, the importance of precise knowledge of miRNA functions cannot be underestimated, not only from a scientific point of view, but also from a clinical perspective to make the most of such drugs and avoid unexpected harmful effects. The aims of this review are to describe current knowledge regarding both known and as-yet-undiscovered molecular aspects of the biological roles of miRNAs in the liver, with a special emphasis on lipid, glucose, drug, and iron metabolism as vital functions of the liver as well as important therapeutic targets.
微小RNA(miRNA)是一类小的非编码RNA分子,它们通过与数千种信使RNA进行互补碱基配对,在转录后水平调节基因表达。尽管单个miRNA的靶基因和精确生物学功能在很大程度上仍不清楚,但推测miRNA在正常和病理状态下的多种生物学过程中发挥重要作用。肝脏是一个重要器官,在许多生理功能中起主要作用。利用基因修饰小鼠或体内核酸递送技术来研究肝脏miRNA,以过表达特定miRNA或抑制miRNA功能,这些研究的最新进展揭示了单个miRNA在体内肝脏生理必需功能中的关键生物学作用。由于基于miRNA的策略正在应用于临床治疗,因此,不仅从科学角度,而且从临床角度充分利用此类药物并避免意外有害影响方面,精确了解miRNA功能的重要性都不可低估。本综述的目的是描述目前关于miRNA在肝脏生物学作用的已知和尚未发现的分子方面的知识,特别强调脂质、葡萄糖、药物和铁代谢作为肝脏的重要功能以及重要治疗靶点。