miRNA-486-5p: signaling targets and role in non-malignant disease.
miRNA-486-5p: signaling targets and role in non-malignant disease.
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DOI：
10.1007/s00018-022-04406-y
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发表时间：
2022-06-22
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microRNA（miRNAs）是一类短的非编码RNA，在物种间高度保守，是基因表达的强有力调控因子。miRNAs的异常表达改变了与人类疾病相关的生物学过程和途径。miR-486- 5 p是位于细胞质和细胞核中的肌肉富集的miRNA，并且在人血浆中高度丰富，并且在小的细胞外囊泡中富集。对恶性和非恶性疾病（包括肾脏疾病）的研究发现了与循环miR-486- 5 p水平的相关性，支持其作为潜在生物标志物的作用。非恶性疾病的临床前研究已经鉴定了调节参与细胞增殖、迁移、血管生成和凋亡的主要信号传导途径的miR-486- 5 p靶标。经验证的miR-486- 5 p靶标包括磷酸酶和张力蛋白同源物（PTEN）和FoXO 1，其抑制激活磷脂酰肌醇-3-激酶（PI 3 K）/Akt信号传导。通过miR-486- 5 p靶向Smad 1/2/4和IGF-1分别抑制转化生长因子（TGF）-β和胰岛素样生长因子-1（IGF-1）信号传导。其他miR-486- 5 p靶点包括基质金属蛋白酶-19（MMP-19）、Sp 5、组蛋白乙酰转移酶1（HAT 1）和活化T细胞核因子-5（NFAT 5）。在这篇综述中，我们研究了miR-486- 5 p在非恶性疾病中的生物起源、调节、验证的基因靶点和生物学效应。在线版本包含补充材料，可通过10.1007/s 00018 -022-04406-y获得。
MicroRNAs (miRNAs) are short non-coding RNAs, highly conserved between species, that are powerful regulators of gene expression. Aberrant expression of miRNAs alters biological processes and pathways linked to human disease. miR-486-5p is a muscle-enriched miRNA localized to the cytoplasm and nucleus, and is highly abundant in human plasma and enriched in small extracellular vesicles. Studies of malignant and non-malignant diseases, including kidney diseases, have found correlations with circulating miR-486-5p levels, supporting its role as a potential biomarker. Pre-clinical studies of non-malignant diseases have identified miR-486-5p targets that regulate major signaling pathways involved in cellular proliferation, migration, angiogenesis, and apoptosis. Validated miR-486-5p targets include phosphatase and tensin homolog (PTEN) and FoXO1, whose suppression activates phosphatidyl inositol-3-kinase (PI3K)/Akt signaling. Targeting of Smad1/2/4 and IGF-1 by miR-486-5p inhibits transforming growth factor (TGF)-β and insulin-like growth factor-1 (IGF-1) signaling, respectively. Other miR-486-5p targets include matrix metalloproteinase-19 (MMP-19), Sp5, histone acetyltransferase 1 (HAT1), and nuclear factor of activated T cells-5 (NFAT5). In this review, we examine the biogenesis, regulation, validated gene targets and biological effects of miR-486-5p in non-malignant diseases. The online version contains supplementary material available at 10.1007/s00018-022-04406-y.
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