2. Academic Validation
  3. The GNL3L-MDM2 Interaction Drives Esophageal Squamous Cell Carcinoma Progression

The GNL3L-MDM2 Interaction Drives Esophageal Squamous Cell Carcinoma Progression

  • Cancer Med. 2025 Sep;14(17):e71146. doi: 10.1002/cam4.71146.
Aijie Yang 1,  Haiyun Song 2,  Yufeng Cheng 3
Affiliations

Affiliations

  • 1 Department of Radiotherapy, Qilu Hospital of Shandong University (Qingdao), Qingdao, China.
  • 2 Department of Pathology, Qilu Hospital of Shandong University (Qingdao), Qingdao, China.
  • 3 Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China.
PMID: 40856423 DOI: 10.1002/cam4.71146
Abstract

Background: This study investigates the mechanisms by which GNL3L influences ESCC progression.

Methods: GNL3L expression was analyzed via immunohistochemistry in ESCC tissues. Cell proliferation (EdU and CCK8 assays), migration, invasion (wound healing and Transwell assays), cell cycle, and Apoptosis (flow cytometry) were assessed. Levels of GNL3L, MDM2, p53, and p21 were evaluated by qRT-PCR and western blot. Tumor growth was observed in nude mice injected with TE-1 cells.

Results: GNL3L was upregulated in ESCC specimens (p < 0.05) and knockdown reduced proliferation and migration while enhancing Apoptosis (p < 0.01). GNL3L interacted with MDM2; knocking down GNL3L decreased MDM2 and increased p53 and p21 (p < 0.01). MDM2 overexpression enhanced malignant characteristics, reversible by GNL3L silencing (p < 0.01). Moreover, MDM2 knockdown inhibited malignant characteristics, reversible by GNL3L overexpression (p < 0.01). In vivo, the sh-GNL3L group exhibited the smallest tumor volumes after 5 weeks (p < 0.01).

Conclusions: GNL3L correlates with ESCC malignancy, influencing the MDM2-p53-p21 axis. GNL3L-MDM2 interaction is critical in ESCC progression.

Keywords

GNL3L; MDM2; apoptosis; esophageal squamous cell carcinoma; invasion; proliferation.

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