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miRNA-486-5p：信号靶标及其在非恶性疾病中的作用。

miRNA-486-5p: signaling targets and role in non-malignant disease.

机构信息

Division of Nephrology, Department of Medicine and Kidney Research Centre, The Ottawa Hospital Research Institute, University of Ottawa, 1967 Riverside Dr., Rm. 535, Ottawa, ON, K1H 7W9, Canada.

Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.

出版信息

Cell Mol Life Sci. 2022 Jun 22;79(7):376. doi: 10.1007/s00018-022-04406-y.

DOI:10.1007/s00018-022-04406-y
PMID:35731367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9217846/
Abstract

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.

摘要

微小 RNA（miRNAs）是一种短的非编码 RNA，在物种间高度保守，是基因表达的强大调节因子。miRNAs 的异常表达会改变与人类疾病相关的生物过程和途径。miR-486-5p 是一种富含肌肉的 miRNA，定位于细胞质和细胞核，在人血浆中高度丰富，并富含小细胞外囊泡。对包括肾脏疾病在内的恶性和非恶性疾病的研究发现，与循环 miR-486-5p 水平相关，支持其作为潜在生物标志物的作用。对非恶性疾病的临床前研究确定了 miR-486-5p 的靶标，这些靶标调节细胞增殖、迁移、血管生成和凋亡等主要信号通路。已验证的 miR-486-5p 靶标包括磷酸酶和张力蛋白同源物（PTEN）和 FoxO1，其抑制物激活磷脂酰肌醇-3-激酶（PI3K）/Akt 信号通路。miR-486-5p 靶向 Smad1/2/4 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）信号通路。miR-486-5p 的其他靶标包括基质金属蛋白酶-19（MMP-19）、Sp5、组蛋白乙酰转移酶 1（HAT1）和激活的 T 细胞核因子-5（NFAT5）。在这篇综述中，我们检查了非恶性疾病中 miR-486-5p 的生物发生、调节、已验证的基因靶标和生物学效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5364/11071899/0c7de9c98a38/18_2022_4406_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5364/11071899/e32a5f9ee34e/18_2022_4406_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5364/11071899/629a10ae67a2/18_2022_4406_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5364/11071899/bf020be4b993/18_2022_4406_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5364/11071899/0c7de9c98a38/18_2022_4406_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5364/11071899/e32a5f9ee34e/18_2022_4406_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5364/11071899/629a10ae67a2/18_2022_4406_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5364/11071899/bf020be4b993/18_2022_4406_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5364/11071899/0c7de9c98a38/18_2022_4406_Fig4_HTML.jpg

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