LINC00312 increases gemcitabine sensitivity in nasopharyngeal carcinoma by recruiting PABPC1 and modulating PAX5-mediated transcription of LPLUNC1

  • NPJ Precis Oncol. 2026 Jun 17. doi: 10.1038/s41698-026-01542-7.
Zhen Guo  1  2  3 ,  ZhiMin Zhang  4 ,  Huai Liu  5 ,  Feng Liu  5 ,  Pan Chen  5 ,  BinSheng He  1  2  6 ,  Hui Wang  7 ,  JiaoYang Lu  8  9  10
Affiliations
  • 1. Hunan Provincial Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, the First Clinical College and the First Affiliated Hospital of Changsha Medical University, Changsha Medical University, Changsha, China.
  • 2. Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, China.
  • 3. Hunan Provincial Key Laboratory of the Fundamental and Clinical Research on Multimodal Oncology, the First Clinical College and the First Affiliated Hospital of Changsha Medical University, Changsha Medical University, Changsha, China.
  • 4. Department of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
  • 5. Hunan Key Laboratory of Translational Radiation Oncology, Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
  • 6. Hunan Provincial Key Laboratory of the Regional Characteristic Traditional Chinese Medicine Resources and Ecological Agriculture, Changsha Medical University, Changsha, China.
  • 7. Hunan Key Laboratory of Translational Radiation Oncology, Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. [email protected].
  • 8. Hunan Provincial Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, the First Clinical College and the First Affiliated Hospital of Changsha Medical University, Changsha Medical University, Changsha, China. [email protected].
  • 9. Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, China. [email protected].
  • 10. Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, Changsha, China. [email protected].
PMID: 42310073 DOI: 10.1038/s41698-026-01542-7
Abstract

Gemcitabine resistance is an important factor in the treatment failure of nasopharyngeal carcinoma (NPC). LINC00312 has been reported to associate with chemotherapy toxicity and chemoradiotherapy response in NPC. However, the molecular mechanism by which LINC00312 regulates NPC sensitivity to gemcitabine is unclear. We found overexpression of LINC00312 or LPLUNC1 inhibited NPC cell proliferation, migration, invasion, and increased gemcitabine sensitivity. Mechanistically, LINC00312 bound to PABPC1 to increase PAX5 mRNA stability. PAX5 transcriptionally activated LPLUNC1 to inhibit the malignant phenotype of NPC and increase gemcitabine sensitivity. PAX5 depletion diminished the inhibitory effects of gemcitabine on cell viability, while LPLUNC1 overexpression restored chemosensitivity. Furthermore, PAX5 interacted with LINC00312 promoter to transcriptionally activate LINC00312. In turn, the LINC00312-PAX5 feedback axis upregulated LPLUNC1 to inhibit the progression of NPC and increase gemcitabine sensitivity in NPC. In conclusion, LINC00312 increased PAX5 mRNA stability by recruiting PABPC1, which promoted LPLUNC1 transcription to regulate sensitivity of NPC to gemcitabine. Meanwhile, PAX5 in turn transcriptionally activated LINC00312 to form a feedback axis, which further increased gemcitabine sensitivity.

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