2. Academic Validation
  3. 8q24 derived ZNF252P promotes tumorigenesis by driving phase separation to activate c-Myc mediated feedback loop

8q24 derived ZNF252P promotes tumorigenesis by driving phase separation to activate c-Myc mediated feedback loop

  • Nat Commun. 2025 Feb 26;16(1):1986. doi: 10.1038/s41467-025-56879-7.
Tianyu Qu # 1,  Chang Zhang # 2 3,  Xiyi Lu # 1,  Jiali Dai # 1,  Xuezhi He 4,  Wei Li 1,  Liang Han 5,  Dandan Yin 6,  Erbao Zhang 7 8
Affiliations

Affiliations

  • 1 Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
  • 2 Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
  • 3 The Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
  • 4 Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
  • 5 Department of Oncology, Xuzhou Central Hospital, Xuzhou School of Clinical Medicine of Nanjing Medical University, Xuzhou, Jiangsu, PR China. hanliang_njmu@sina.com.
  • 6 Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Zhong Fu Road, Gulou District, Nanjing, Jiangsu, 210003, PR China. jsnydandan@sina.com.
  • 7 Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. erbaozhang@njmu.edu.cn.
  • 8 Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China. erbaozhang@njmu.edu.cn.
  • # Contributed equally.
PMID: 40011431 DOI: 10.1038/s41467-025-56879-7
Abstract

As a well-known Cancer risk region, the 8q24 locus is frequently amplified in a variety of solid tumors. Here we identify a pseudogene-derived oncogenic lncRNA, ZNF252P, which is upregulated in a variety of Cancer types by copy number gain as well as c-Myc-mediated transcriptional activation. Mechanistically, ZNF252P binds and drives "phase separation" of HNRNPK and ILF3 protein in the nucleus and cytoplasm, respectively, to transcriptionally and posttranscriptionally activate c-Myc, thus forming a c-Myc/ZNF252P/c-Myc positive feedback loop. These findings expand the understanding of the relationship between genomic instability in the 8q24 region and tumorigenesis and clarify a regulatory mechanism involved in transcription and posttranscription from the perspective of RNA-mediated nuclear and cytoplasmic protein phase separation, which sheds light on the dialogue with the driver oncogene c-Myc. The pivotal regulatory axis of ZNF252P/c-Myc has potential as a promising biomarker and therapeutic target in Cancer development.

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