2. Academic Validation
  3. NME2 modulates HCC progression through 4EBP1 phosphorylation and autophagy regulation independent of mTOR

NME2 modulates HCC progression through 4EBP1 phosphorylation and autophagy regulation independent of mTOR

  • Hepatol Commun. 2025 Jun 9;9(7):e0715. doi: 10.1097/HC9.0000000000000715.
Wei Chen 1,  Da-Chen Zhou 2,  Chen-Hui Rui 2,  Rong Wang 3,  Sheng-Liang Shan 4,  Jiang-Ming Chen 4,  Wen-Wu Luo 5,  Xiao Cui 2,  Hui Hou 2,  Fu-Bao Liu 4
Affiliations

Affiliations

  • 1 Department of General Surgery, The Second People's Hospital of Hefei, Anhui, China.
  • 2 Department of Liver Transplantation, The Second Affiliated Hospital of Anhui Medical University, Anhui, China.
  • 3 Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
  • 4 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
  • 5 Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
PMID: 40489759 DOI: 10.1097/HC9.0000000000000715
Abstract

Background: To investigate the role of nucleoside diphosphate kinase 2 (NME2) in HCC progression, assessing its therapeutic potential.

Methods: Utilizing transcriptome Sequencing data from The Cancer Genome Atlas (TCGA) and immunohistochemical staining of tissue microarrays, we analyzed NME2 expression in HCC tumor tissues. The effects of NME2 on HCC cell proliferation and Autophagy flux were assessed through knockdown and overexpression experiments. Additionally, the relationship between NME2 and 4EBP1 phosphorylation was explored through specific site mutation analysis.

Results: NME2 overexpression in HCC correlated with poor prognosis. NME2 knockdown significantly hindered HCC cell proliferation and induced Autophagy flux. Notably, NME2 modulates 4EBP1 phosphorylation (Thr37/46) independently of mTOR, unveiling a novel axis in HCC pathogenesis. Additionally, NME2 modulates eukaryotic translation initiation factor 4F (eIF4F) complex formation and Autophagy flux.

Conclusions: NME2 plays a crucial role in HCC development by modulating 4EBP1 phosphorylation and Autophagy through an mTOR-independent pathway. Our research underscores NME2's significance as a potential therapeutic target in HCC, meriting further exploration of its underlying mechanisms and clinical applicability.

Keywords

HCC; autophagy flux; cell proliferation; eIF4F complex formation; mTOR-independent mechanism.

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