Yin Qian, Yao Yinye, Ni Jiaojiao, Zhang Yiwen, Wu Jia, Zeng Hui, Wu Wei, Zhuo Wei, Ying Jieer, Li Jingjing
Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, 310022, Zhejiang, China.
Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Hangzhou Institute of Medicine (HIM), Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, P. R. China.
Mol Med. 2025 Feb 20;31(1):71. doi: 10.1186/s10020-025-01125-5.
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.
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.
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.
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.
代谢重编程是肝细胞癌（HCC）进展的一个标志，它驱使细胞对病理刺激产生异常的细胞过程。虽然二氢硫辛酰胺转乙酰基酶（DLAT）已被认为与多种癌症的发生有关，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、功能及作用机制。
利用RNA测序数据、组织芯片、体外和体内功能试验以及机制研究进行综合分析，以评估DLAT的表达、其在肿瘤进展中的功能作用以及HCC相关的分子途径。
我们的研究显示HCC中DLAT表达显著上调，这与预后不良有关。此外，我们发现DLAT通过驱动HCC细胞的代谢重编程促进肿瘤转移。机制上，发现DLAT通过H3K18乙酰化增强葡萄糖转运蛋白1（GLUT1）的表达，从而促进有氧糖酵解和上皮-间质转化（EMT），进而在体外和体内增强HCC的转移。最后，我们证实了HCC组织中DLAT与GLUT1表达之间呈正相关。
这些发现确立了DLAT作为HCC进展的关键调节因子，并表明其作为改善HCC诊断和治疗的有前景的预测生物标志物和治疗靶点的潜力。
