Recent advances of miR-23 in human diseases and growth development

Abstract

MicroRNA (miRNA) is broadly manifested in eukaryotes and serves as a critical function in biological development and disease occurrence. With the rapid advancement of experimental research tools, researchers have discovered functional correlations among different miRNA isoforms and clusters within the same miRNA family. As a highly conserved member in the miR-23-27-24 cluster, miR-23 exhibits different isoforms and participates in various essential development. Although the miR-23-27-24 cluster has overlapping target sites, their differential expression can demonstrate independent biological functions. Furthermore, the untapped effects of miR-23 on organisms, whether as a functional cluster or a single regulator, has not been systematically elucidated yet. In this review article, we analyze the genomic location of miR-23 and its sequence variances among its isoforms or family members while summarizing its regulatory functions in metabolic diseases, immune responses, cardiovascular diseases, cancer, organ development as well as nervous system function. This review highlights the significant role of miR-23 as a biomarker for disease diagnosis and a key regulatory factor in pathogenesis, which can help us comprehend the diverse functions of miRNAs and provide a theoretical reference for the functional differences among miRNA isoforms.

Keywords: Cancer; Disease; Immunity; Metabolism; miR-23.

Fig. 1

Conservative analysis of miR-23 mature sequence. (A–D) The genome location of mir-23 in Mus musculus. (E–H) The miR-23a/b sequences alignment analysis of Danio rerio, Xenopus tropicalis, Anolis carolinensis, Equus caballus, Mus musculus, Rattus norvegicus, Gorilla, Homo sapiens were performed in Vector NTI software. The sequences data were obtained in NCBI and miRbase (https://mirbase.org/hairpin/MI0000079).

Fig. 2

The diagram depicts the complex functions and interactions of miR-23 in immunity. By affecting specialized immune cells such as Langerhans cells, T cells and Macrophage cells through various signaling mechanisms, miR-23 representing its contributions to the maintenance of the intestinal barrier, vascular barrier and Renal inflammatory. LncRNA Malat1 and Oasl2-209 displayed a competitive binding to miR-23 thereby involved in regulating immune processes. The overall color scheme of red and green highlights their different functional aspects. Bio-render was used to construct this networks (https://www.biorender.com/library).

Fig. 3

The pivotal regulatory functions of miR-23 in brain and vascular cells. Specifically, the brain is mainly regulated by miR-23a-5p and miR-23a-3p, such as participating in CVEC apoptosis, and promoting brain recovery by enhancing cell activity and hemoglobin integrity. Moreover, miR-23a/b regulates cell cycle progression, maintaining vascular balance and fostering endothelial progenitor cell activity. In vascular cells, miR-23a/b inhibits apoptosis and stimulates vascular smooth muscle cell growth, promoting angiogenesis and endothelial function. Furthermore, it modulates mitochondrial autophagy and glutathione metabolism by targeting Sprouty2, ultimately restoring cellular metabolism. These intricate regulatory mechanisms underscore the significance of miR-23 in preserving brain function and vascular health. The figure was drawn by Figdraw (https://www.figdraw.com).

Fig. 4

The intricate signaling pathways and functional networks of miR-23 in tumor cell biology. miR-23a and miR-23b regulate various genes and pathways that affect tumor development and progression. Key pathways depicted include the p65/miR-23a/CCL22 axis, the PTEN/PI3K/Akt signaling pathway, the Wnt/β-catenin signaling pathway, and mitochondrial dysfunction mediated by GLS. The isoforms of miR-23 displayed different expression patterns in HCC, OC and lymphoma cells, but can all affect tumor growth. miR-23a undertake more roles in promotes tumor growth through multiple mechanisms, including its regulation of tumor proliferation and metastasis, cell cycle progression, and microvascular proliferation. The diagram also highlights the involvement of lncRNAs, such as LINC00909 Malat1 and MEG3, in modulating miR-23a/23b function and tumor behavior. Moreover, the interactions between miR-23a/23b and genes like NF-κB, β-catenin, p16/CDH13, and KEAP1 suggest their importance in tumor cell proliferation, invasion, and drug resistance. This figure was drawn by Figdraw (https://www.figdraw.com).

Fig. 5

Functional roles of miR-23 in organ development. This diagram illustrates the diverse functional roles of miR-23 in regulating various biological processes during organ development. Each circle represents the interaction genes and related pathways of miR-23 in different organs, which are displayed in yellow, red, green, purple, and blue for uterus, heart, skeleton, tooth, and pituitary tissues. The research on miR-23 in the skeleton is the most extensive among all the organs shown in the figure. This figure was drawn by Figdraw (https://www.figdraw.com).