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解读17-β-羟基类固醇脱氢酶4:从分子洞察到癌症治疗

Deciphering 17-β-hydroxysteroid dehydrogenase 4: from molecular insights to cancer therapeutics.

作者信息

Liao Meng-Bin, Lau Andy T Y, Xu Yan-Ming

机构信息

The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong, People's Republic of China.

Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, 515041, Guangdong, People's Republic of China.

出版信息

Cancer Cell Int. 2025 Jul 19;25(1):273. doi: 10.1186/s12935-025-03885-w.

DOI:10.1186/s12935-025-03885-w
PMID:40684154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12276699/
Abstract

17-β-hydroxysteroid dehydrogenase 4 (HSD17B4), abundantly present in the peroxisomal regions of mammalian cells, is an oxidoreductase that catalyzes the oxidoreduction of steroid substrates. Impairment of lipid metabolism represents one of the most critical metabolic alterations in cancer, with lipid metabolic processes tightly linked to tumor cell proliferation, survival, invasion, and metastasis. HSD17B4 is primarily involved in the regulation of cellular fatty acid and hormone metabolism. Therefore, HSD17B4 is closely related to tumors, but few relevant studies exist. Polymorphisms and methylation of the HSD17B4 gene, as well as acetylation of the HSD17B4 protein, influence its expression and function, impacting cancer progression and therapeutic response. Recent findings also highlight HSD17B4 as a potential therapeutic target and prognostic biomarker in various cancers. Here, we will discuss the latest literature on human HSD17B4 and its clinical implications.

摘要

17-β-羟基类固醇脱氢酶4(HSD17B4)大量存在于哺乳动物细胞的过氧化物酶体区域,是一种催化类固醇底物氧化还原反应的氧化还原酶。脂质代谢受损是癌症中最关键的代谢改变之一,脂质代谢过程与肿瘤细胞的增殖、存活、侵袭和转移密切相关。HSD17B4主要参与细胞脂肪酸和激素代谢的调节。因此,HSD17B4与肿瘤密切相关,但相关研究较少。HSD17B4基因的多态性和甲基化,以及HSD17B4蛋白的乙酰化,会影响其表达和功能,进而影响癌症进展和治疗反应。最近的研究结果还突出了HSD17B4作为各种癌症潜在治疗靶点和预后生物标志物的作用。在此,我们将讨论关于人类HSD17B4的最新文献及其临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea56/12276699/835fe48c8af0/12935_2025_3885_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea56/12276699/835fe48c8af0/12935_2025_3885_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea56/12276699/94b3f83f252b/12935_2025_3885_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea56/12276699/1b07deb0843b/12935_2025_3885_Fig2a_HTML.jpg
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本文引用的文献

1
Hydroxysteroid 17-β dehydrogenase 14 (HSD17B14) is an L-fucose dehydrogenase, the initial enzyme of the L-fucose degradation pathway.羟类固醇 17-β 脱氢酶 14(HSD17B14)是一种 L-岩藻糖脱氢酶,是 L-岩藻糖降解途径的初始酶。
J Biol Chem. 2024 Aug;300(8):107501. doi: 10.1016/j.jbc.2024.107501. Epub 2024 Jun 27.
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A novel proteomic-based model for predicting colorectal cancer with Schistosoma japonicum co-infection by integrated bioinformatics analysis and machine learning.基于蛋白质组学的新型模型,通过整合生物信息学分析和机器学习预测日本血吸虫感染的结直肠癌。
BMC Med Genomics. 2023 Oct 30;16(1):269. doi: 10.1186/s12920-023-01711-8.
3
Targeting sex steroid biosynthesis for breast and prostate cancer therapy.
针对性类固醇生物合成进行乳腺癌和前列腺癌治疗。
Nat Rev Cancer. 2023 Sep 8. doi: 10.1038/s41568-023-00609-y.
4
HSD17B4 methylation enhances glucose dependence of BT-474 breast cancer cells and increases lapatinib sensitivity.HSD17B4 甲基化增强了 BT-474 乳腺癌细胞对葡萄糖的依赖性,并增加了拉帕替尼的敏感性。
Breast Cancer Res Treat. 2023 Sep;201(2):317-328. doi: 10.1007/s10549-023-07013-y. Epub 2023 Jun 28.
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High expression of peroxisomal D-bifunctional protein in cytosol regulates apoptosis and energy metabolism of hepatocellular carcinoma cells via PI3K/AKT pathway.过氧化物酶体D-双功能蛋白在胞浆中的高表达通过PI3K/AKT途径调节肝癌细胞的凋亡和能量代谢。
Am J Cancer Res. 2023 May 15;13(5):1884-1903. eCollection 2023.
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17β-hydroxysteroid dehydrogenases in the progression of nonalcoholic fatty liver disease.17β-羟甾类脱氢酶在非酒精性脂肪性肝病进展中的作用。
Pharmacol Ther. 2023 Jun;246:108428. doi: 10.1016/j.pharmthera.2023.108428. Epub 2023 Apr 26.
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A prediction model for prognosis of gastric adenocarcinoma based on six metabolism-related genes.基于六个代谢相关基因的胃腺癌预后预测模型
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CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763.
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