LINC-AC092535.5 regulates MICAL2 mRNA level to inhibit p53-mediated ferroptosis in nasopharyngeal carcinoma

  • Oncogene. 2026 Apr;45(14):1260-1274. doi: 10.1038/s41388-026-03714-y.
Siyu Zhang  #  1 ,  Wenyue Chen  #  1 ,  Ji Yang  1 ,  Zhen Ge  1 ,  Yan Kong  2 ,  Haiou Yan  3 ,  Lili Bao  1 ,  Ying Shan  1 ,  Zhiyuan Yang  1 ,  Wenhui Chen  1 ,  Si Pan  1 ,  Yiwen You  1 ,  Bo You  4 ,  Qicheng Zhang  5
Affiliations
  • 1. Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
  • 2. The PRC Ministry of Education Engineering Research Center of Intelligent Technology for Healthcare, Wuxi, China.
  • 3. Department of Nursing, Affiliated Hospital of Nantong University, Nantong, China.
  • 4. Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China. [email protected].
  • 5. Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China. [email protected].
  • # Contributed equally.
PMID: 41832266 DOI: 10.1038/s41388-026-03714-y
Abstract

Ferroptosis is a form of iron-dependent programmed cell death (PCD) that, once activated, inhibits tumor progression. However, the specific mechanisms influencing Ferroptosis in nasopharyngeal carcinoma (NPC) are limited and warrant further investigation. This study proposes that MICAL2 not only influences the nuclear translocation of p53 but also facilitates the ubiquitination of p53 by recruiting the E3 ubiquitination Ligase MDM2, leading to its degradation. This process inhibits Ferroptosis in NPC cells, thereby promoting NPC progression and adversely affecting the prognosis of NPC patients. Additionally, we identified a novel long non-coding RNA (lncRNA), LINC-AC092535.5, which directly modulates the MICAL2 mRNA level through dual reinforcement at both transcriptional and post-transcriptional levels. Transcriptome Sequencing and RACE experiments provided insights into the function of this new lncRNA. These findings will contribute to the expansion of the Ferroptosis gene regulatory network and inform new clinical treatment strategies for NPC.

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