DLAT activates EMT to promote HCC metastasis by regulating GLUT1-mediated aerobic glycolysis.

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Medicine Pub Date : 2025-02-20 DOI:10.1186/s10020-025-01125-5

Qian Yin, Yinye Yao, Jiaojiao Ni, Yiwen Zhang, Jia Wu, Hui Zeng, Wei Wu, Wei Zhuo, Jieer Ying, Jingjing Li

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引用次数: 0

Abstract

Background: Metabolic reprogramming is a hallmark of hepatocellular carcinoma (HCC) progression, driving aberrant cellular processes in response to pathological stimuli. While dihydrolipoyl transacetylase (DLAT) has been implicated in the development of various cancers, its specific role and underlying mechanisms in HCC remain unclear. This study aimed to investigate the expression, function, and mechanistic impact of DLAT in HCC.

Methods: A comprehensive analysis was conducted using RNA sequencing data, tissue microarrays, in vitro and in vivo functional assays, and mechanistic studies to evaluate DLAT expression, its functional role in tumor progression, and associated molecular pathways in HCC.

Results: Our study revealed a significant upregulation of DLAT expression in HCC, which was linked to a poor prognosis. Furthermore, we discovered that DLAT facilitated tumor metastasis by driving metabolic reprogramming in HCC cells. Mechanistically, DLAT was found to enhance glucose transporter 1 (GLUT1) expression via H3K18 acetylation, thereby promoting aerobic glycolysis and epithelial-to-mesenchymal transition (EMT), which subsequently augmented metastasis of HCC both in vitro and in vivo. Finally, we confirmed a positive correlation between DLAT and GLUT1 expression in HCC tissues.

Conclusions: These findings establish DLAT as a key regulator in HCC progression and suggest its potential as a promising predictive biomarker and therapeutic target for improving HCC diagnosis and treatment.

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背景：代谢重编程是肝细胞癌（HCC）进展的一个标志，它驱动异常的细胞过程以应对病理刺激。虽然二氢脂酰基转乙酰酶（DLAT）与多种癌症的发展有关联，但其在 HCC 中的具体作用和潜在机制仍不清楚。本研究旨在探讨 DLAT 在 HCC 中的表达、功能和机制影响：采用 RNA 测序数据、组织芯片、体外和体内功能测试以及机理研究等方法进行了综合分析，以评估 DLAT 在 HCC 中的表达、其在肿瘤进展中的功能作用以及相关分子通路：结果：我们的研究发现，DLAT在HCC中的表达明显上调，这与预后不良有关。此外，我们还发现 DLAT 通过驱动 HCC 细胞的代谢重编程促进肿瘤转移。从机理上讲，我们发现 DLAT 可通过 H3K18 乙酰化增强葡萄糖转运体 1（GLUT1）的表达，从而促进有氧糖酵解和上皮细胞向间质转化（EMT），进而增强 HCC 在体外和体内的转移。最后，我们证实了 DLAT 和 GLUT1 在 HCC 组织中的表达呈正相关：这些发现确定了 DLAT 是 HCC 进展过程中的一个关键调节因子，并表明它有潜力成为一种有前途的预测性生物标记物和治疗靶点，以改善 HCC 的诊断和治疗。

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

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.