Identification of novel therapeutic targets in hepatitis-B virus-associated membranous nephropathy using scRNA-seq and machine learning.

IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Yongzheng Hu, Qian An, Xinxin Yu, Wei Jiang
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Abstract

Hepatitis B Virus-associated membranous nephropathy (HBV-MN) significantly impacts renal health, particularly in areas with high HBV prevalence. Understanding the molecular mechanisms underlying HBV-MN is crucial for developing effective therapeutic strategies. This study aims to elucidate the roles of miR-223-3p and CRIM1 in HBV-MN using single-cell RNA sequencing (scRNA-seq) and machine learning. scRNA-seq analysis identified a distinct subcluster of podocytes linked to HBV-MN progression. miR-223-3p emerged as a critical regulatory molecule, with overexpression resulting in decreased CRIM1 expression. Dual-luciferase reporter assays confirmed miR-223-3p targeting CRIM1 at a conserved binding site. These findings were corroborated by machine learning models, which highlighted the significance of miR-223-3p and CRIM1 in disease pathology. miR-223-3p plays a pivotal role in modulating CRIM1 expression in HBV-MN, providing a potential therapeutic target. Integrating scRNA-seq with machine learning offers valuable insights into the molecular landscape of HBV-MN, paving the way for novel interventions.

利用scRNA-seq和机器学习鉴定乙型肝炎病毒相关膜性肾病的新治疗靶点
乙型肝炎病毒相关膜性肾病(HBV- mn)显著影响肾脏健康,特别是在HBV高流行地区。了解HBV-MN的分子机制对于制定有效的治疗策略至关重要。本研究旨在通过单细胞RNA测序(scRNA-seq)和机器学习来阐明miR-223-3p和CRIM1在HBV-MN中的作用。scRNA-seq分析确定了一个与HBV-MN进展相关的足细胞亚群。miR-223-3p成为关键调控分子,过表达导致CRIM1表达降低。双荧光素酶报告基因检测证实miR-223-3p在一个保守的结合位点靶向CRIM1。这些发现得到了机器学习模型的证实,强调了miR-223-3p和cri1在疾病病理中的意义。miR-223-3p在HBV-MN中调节CRIM1表达中起关键作用,提供了一个潜在的治疗靶点。将scRNA-seq与机器学习相结合,为了解HBV-MN的分子格局提供了有价值的见解,为新的干预措施铺平了道路。
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来源期刊
Scientific Reports
Scientific Reports Natural Science Disciplines-
CiteScore
7.50
自引率
4.30%
发文量
19567
审稿时长
3.9 months
期刊介绍: We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
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