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

IF 5.6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology Communications Pub Date : 2025-06-09 eCollection Date: 2025-07-01 DOI:10.1097/HC9.0000000000000715

Wei Chen, Da-Chen Zhou, Chen-Hui Rui, Rong Wang, Sheng-Liang Shan, Jiang-Ming Chen, Wen-Wu Luo, Xiao Cui, Hui Hou, Fu-Bao Liu

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引用次数: 0

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.

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NME2通过4EBP1磷酸化和独立于mTOR的自噬调节HCC进展。

背景：研究核苷二磷酸激酶2 （NME2）在HCC进展中的作用，评估其治疗潜力。方法：利用肿瘤基因组图谱（TCGA）转录组测序数据和组织芯片免疫组化染色，分析NME2在HCC肿瘤组织中的表达。通过敲低和过表达实验评估NME2对HCC细胞增殖和自噬通量的影响。此外，通过特异性位点突变分析，探讨了NME2与4EBP1磷酸化之间的关系。结果：NME2在HCC中过表达与预后不良相关。NME2敲低显著抑制HCC细胞增殖，诱导细胞自噬通量。值得注意的是，NME2独立于mTOR调节4EBP1磷酸化（Thr37/46），揭示了HCC发病机制的新轴。此外，NME2调节真核生物翻译起始因子4F （eIF4F）复合物的形成和自噬通量。结论：NME2通过mtor独立通路调节4EBP1磷酸化和自噬，在HCC的发展中起着至关重要的作用。我们的研究强调了NME2作为HCC潜在治疗靶点的重要性，值得进一步探索其潜在机制和临床适用性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hepatology Communications GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

8.00

自引率

2.00%

发文量

248

审稿时长

8 weeks

期刊介绍： Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction.