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

Journal: Scientific reports
Published Date:

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.

Authors

  • Yongzheng Hu
    Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
  • Qian An
    Department of Nephrology, Qingdao Central Hospital, Qingdao, Shandong, China.
  • Xinxin Yu
    Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
  • Wei Jiang
    Department of Civil Engineering, Johns Hopkins System Institute, Johns Hopkins University, Baltimore, Maryland.