2. Academic Validation
  3. CircRNA-encoded RIPK1-98 protein drives lung adenocarcinoma progression

CircRNA-encoded RIPK1-98 protein drives lung adenocarcinoma progression

  • Dev Cell. 2026 May 13;61(5):1092-1110.e12. doi: 10.1016/j.devcel.2026.02.014.
Qi Sun 1,  Runqiu Chi 2,  Xiao Zhang 1,  Tianxiang Chen 3,  Xin Xu 1,  Lifang Ma 4,  Xiaoting Tian 1,  Yayou Miao 1,  Yongchun Yu 1,  Rui Kang 5,  Guido Kroemer 6,  Yi Shi 7,  Daolin Tang 8,  Jiayi Wang 9
Affiliations

Affiliations

  • 1 Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai 200030, China.
  • 2 Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai 200030, China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai 200030, China.
  • 3 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
  • 4 Department of Clinical Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
  • 5 Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
  • 6 Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Institut Universitaire de France, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France; Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
  • 7 Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: [email protected].
  • 8 Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: [email protected].
  • 9 Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai 200030, China; Department of Clinical Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Faculty of Medical Laboratory Science, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: [email protected].
PMID: 41825439 DOI: 10.1016/j.devcel.2026.02.014
Abstract

Unexplored biological matter-including uncharacterized genetic elements, molecular entities, and microbial components-remains poorly understood. Here, we use integrated multi-omics approaches to identify and characterize previously unrecognized protein products encoded by circular RNAs (circRNAs) in human tissue specimens and to delineate their roles in the progression of lung adenocarcinoma (LUAD). The transcription of precursor mRNA by RNA polymerase Ⅱ subunit A (RPB1) is crucial for the biogenesis of these potential circRNA-encoded proteins. Functional and translational analyses link their expression to distinct pathological stages of LUAD in patients. The protein RIPK1-98, encoded by circRIPK1, was identified as functionally distinct from its parental gene product, receptor-interacting serine/threonine kinase 1 (RIPK1). RIPK1-98 modulates cyclin-dependent kinase 2 (CDK2)-dependent cell-cycle regulation, thereby facilitating tumor proliferation in cellular and animal models. Together, these findings suggest that RIPK1-98 serves as a biomarker for cell-cycle progression in LUAD and highlight its potential as a therapeutic target to counteract resistance to first-line treatments, such as osimertinib.

Keywords

cell cycle; circRNA-encoded protein; lung adenocarcinoma; protein translation; targeted therapy.

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