Identifying the crucial oncogenic mechanisms of DDX56 based on a machine learning-based integration model of RNA-binding proteins.

Journal: NPJ precision oncology
Published Date: Jul 17, 2025

Abstract

RNA-binding proteins (RBPs) play a fundamental role in cellular metabolism, with their disturbance leading to large-scale transcriptomic dysregulation. RBP dysregulation is highly prevalent in human cancers; however, its role in lung adenocarcinoma (LUAD) has not been systematically investigated. To establish a more effective and robust risk model, a machine learning integration program was used to screen hub prognostic RBPs. Our risk model C-index performed extremely well among 103 published signatures. The high-risk group had a lower immune score and worse immunotherapy effects. As one of the members of the RNA helicase family, DDX56 can interact with certain transcription factors, thereby regulating the expression of its downstream targets. DDX56 exerts an anti-apoptotic effect and reduces the sensitivity to carboplatin treatment by promoting Bcl-2 transcription in LUAD cells. Additionally, DDX56 activates NF-kB signaling pathways, which may be related to DDX56-mediated promotion of Bcl-2 transcription, proliferation, migration, and invasion in LUAD patients.

Authors

  • Hui Jiang
    Queensland Alliance for Environmental Health Science (QAEHS), University of Queensland, 20 Cornwall Street, Woolloongabba, QLD 4012, Australia.
  • Haotian Zheng
    State Key Joint Laboratory of Environmental Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China.
  • Xinjie Zhao
    College of Humanities and Development Studies, China Agricultural University, Beijing 100083, PR China. Electronic address: sinketsuzao@foxmail.com.
  • Yunzhi Xiang
    Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • Jiahao Li
  • Kai Wang
    Department of Rheumatology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
  • Guanghui Wang
    School of Engineering, University of Kansas, Lawrence, KS, United States of America.
  • Jiajun Du
    Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. dujiajun@sdu.edu.cn.

Keywords

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