GNL3L与MDM2的相互作用推动食管鳞状细胞癌进展。

The GNL3L-MDM2 Interaction Drives Esophageal Squamous Cell Carcinoma Progression.

作者信息

Yang Aijie, Song Haiyun, Cheng Yufeng

机构信息

Department of Radiotherapy, Qilu Hospital of Shandong University (Qingdao), Qingdao, China.

Department of Pathology, Qilu Hospital of Shandong University (Qingdao), Qingdao, China.

出版信息

Cancer Med. 2025 Sep;14(17):e71146. doi: 10.1002/cam4.71146.

DOI:10.1002/cam4.71146

PMID:40856423

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12378702/

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.

摘要

背景

本研究探讨了GNL3L影响食管鳞状细胞癌（ESCC）进展的机制。

方法

通过免疫组织化学分析ESCC组织中GNL3L的表达。评估细胞增殖（EdU和CCK8检测）、迁移、侵袭（伤口愈合和Transwell检测）、细胞周期和凋亡（流式细胞术）。通过qRT-PCR和蛋白质免疫印迹法评估GNL3L、MDM2、p53和p21的水平。在注射TE-1细胞的裸鼠中观察肿瘤生长情况。

结果

GNL3L在ESCC标本中上调（p < 0.05），敲低GNL3L可降低增殖和迁移，同时增强凋亡（p < 0.01）。GNL3L与MDM2相互作用；敲低GNL3L可降低MDM2水平，增加p53和p21水平（p < 0.01）。MDM2过表达增强了恶性特征，GNL3L沉默可使其逆转（p < 0.01）。此外，MDM2敲低抑制了恶性特征，GNL3L过表达可使其逆转（p < 0.01）。在体内，5周后sh-GNL3L组的肿瘤体积最小（p < 0.01）。