2. Academic Validation
  3. ADAR1-HNRNPL-Mediated CircCANX Decline Promotes Autophagy in Chronic Obstructive Pulmonary Disease

ADAR1-HNRNPL-Mediated CircCANX Decline Promotes Autophagy in Chronic Obstructive Pulmonary Disease

  • Adv Sci (Weinh). 2025 May;12(18):e2414211. doi: 10.1002/advs.202414211.
Ting-Ting Chen 1 2,  Yuan-Yuan Wei 1 2,  Jia-Ying Kang 1 2,  Da-Wei Zhang 1 2,  Jing-Jing Ye 1 2,  Xi-Shi Sun 3,  Mei Hong 1 2,  Wen-Ting Zhang 1 2,  Hui-Mei Wu 4,  Zhen-Xing Ding 5,  Guang-He Fei 1 2
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China.
  • 2 Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, Anhui Province, 230022, China.
  • 3 Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, 524000, China.
  • 4 Department of Geriatric Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China.
  • 5 Department of Emergency Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China.
PMID: 40091520 DOI: 10.1002/advs.202414211
Abstract

Chronic obstructive pulmonary disease (COPD) is a characteristic chronic airway inflammatory disease that worsens over time, however, there are currently limited clinical therapeutics to suspend its progression. Circular RNAs (circRNAs), which have emerged as functional regulators in various diseases, including COPD, may server as new pharmacological targets in COPD. Here, it is identified a nuclear circRNA, circCANX, that is preferentially decreased in COPD. The linear splicing of CANX pre-mRNA, enhanced by the ADAR1-HNRNPL interaction, is responsible for the circCANX decline. Clinically, the higher circCANX expression is associated with a worse lung function index of FEV1/FVC among patients with COPD. CircCANX suppresses Autophagy and stress granule (SG) formation to strengthen inflammation of COPD in vivo and in vitro. Mechanistically, circCANX recruits the tumor suppressor protein P53 (P53) mRNA and RNA helicase upstream frameshift 1 (UPF1) to form a ternary complex, which mediates P53 mRNA degradation through nonsense-mediated mRNA decay (NMD) process. Together, this study reveals an important circCANX-mediated regulatory mechanism in COPD, and provides new insights into the potential of circRNA-based drug and biomarker development for COPD.

Keywords

CircCANX; CircRNA biogenesis; autophagy; chronic obstructive pulmonary disease; nonsense‐mediated mRNA decay; stress granule.

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