HSD17B4

Last update 08 May 2025

Basic Info

Synonyms

(3R)-hydroxyacyl-CoA dehydrogenase, 17-beta-HSD 4, 17-beta-hydroxysteroid dehydrogenase 4

+ [13]

Introduction

Bifunctional enzyme acting on the peroxisomal fatty acid beta-oxidation pathway. Catalyzes two of the four reactions in fatty acid degradation: hydration of 2-enoyl-CoA (trans-2-enoyl-CoA) to produce (3R)-3-hydroxyacyl-CoA, and dehydrogenation of (3R)-3-hydroxyacyl-CoA to produce 3-ketoacyl-CoA (3-oxoacyl-CoA), which is further metabolized by SCPx. Can use straight-chain and branched-chain fatty acids, as well as bile acid intermediates as substrates.

100 Clinical Results associated with HSD17B4

100 Translational Medicine associated with HSD17B4

0 Patents (Medical) associated with HSD17B4

310

Literatures (Medical) associated with HSD17B4

01 Jul 2025·Drug Resistance Updates

DTX2 attenuates Lenvatinib-induced ferroptosis by suppressing docosahexaenoic acid biosynthesis through HSD17B4-dependent peroxisomal β-oxidation in hepatocellular carcinoma

Article

Author: Mo, Ke ; Niu, Xing ; Huang, Fuxin ; Shen, Cheng ; Zhang, Zhongyan ; Huang, Shanzhou ; Zhang, Chuanzhao ; Zhou, Qi ; Hou, Baohua ; Li, Zhenchong

AIMSEmerging resistance to Lenvatinib, which is used as a first-line agent for the treatment of advanced hepatocellular carcinoma (HCC), is still a concern. The aim of this study was to determine core factors of Lenvatinib resistance (LR) and their underlying molecular mechanisms.METHODSCRISPR screening in HCC cells was conducted, which identified E3 ubiquitin ligase deltex 2 (DTX2) as a core LR-related gene. In vivo and in vitro models were used to clarify the function of DTX2 on LR and ferroptosis. The upstream regulators and downstream effectors of DTX2 were identified, revealing its complex regulatory network.RESULTSDTX2 promoted anti-ferroptosis in LR HCC cells via downregulating the peroxisomal β-oxidation enzyme HSD17B4. DTX2 induced the ubiquitination-mediated degradation of HSD17B4, resulting in lipid metabolism changes that were associated mainly with docosahexaenoic acid (DHA)-containing PUFAs. Notably, DHA supplements could reverse DTX2-induced anti-ferroptosis and LR. Mechanistically, we uncovered that DTX2 ubiquitinated the HSD17B4 SCP structural domain through its RING structural domain and ubiquitinated the K645 site. The upregulation of DTX2 expression was mediated by JAK2-STAT3 pathway activation. The aberrant activation of STAT3 in acquired LR promoted DTX2 transcription and negatively regulated peroxisomal β-oxidation via K48-ubiquitinated HSD17B4 and decreased DHA-phospholipids levels, leading to the suppression of Lenvatinib-induced ferroptosis in HCC.CONCLUSIONSOur findings suggest that DTX2 attenuates Lenvatinib-induced ferroptosis by inhibiting DHA biosynthesis through HSD17B4-dependent peroxisomal β-oxidation in HCC. The combination of DHA with Lenvatinib could be a promising therapeutic strategy for patients with LR HCC.

01 Feb 2025·Neurological Sciences

HSD17B4 mutation: an unusual cause of cerebellar ataxia

Letter

Author: Lal, Vivek ; Singh, Jagdeep ; Sharma, Ashish ; Kumar, Manoj ; Mehta, Sahil

01 Feb 2025·Current Cancer Drug Targets

Gamma-tocotrienol Inhibits Proliferation and Growth of HSD17B4 Overexpressing HepG2 Liver Cancer Cells

Article

Author: Wang, Yaqi ; Hou, Lianguo ; Yao, Min ; Zhang, Nan ; Liang, Xijia ; Hu, Meng ; Wang, Xiaoming ; Shi, Yun ; Jiang, Lingling

Introduction:Hydroxysteroid 17-beta dehydrogenase 4 (HSD17B4) is involved in the progression of hepatocellular carcinoma (HCC).Aims:This study aimed to investigate the inhibitory effect of gamma-tocotrienol (γ-T3) on the proliferation and growth of HSD17B4-overexpressing HepG2 cells.Methods:HepG2 cells were transfected with empty or HSD17B4-overexpressing plasmids, followed by vitamin E (VE) or γ-T3 treatment. MTS assay, Western blotting, qRT-PCR, and flow cytometry were employed to assess cell proliferation, protein expression, mRNA levels, and apoptosis. HSD17B4 interaction with γ-T3 was assessed by quantifying γ-T3 in the collected precipitate of HSD17B4 using anti-flag magnetic beads. Tumor xenografts were established in NSG mice, and tumor growth was monitored.Results:HSD17B4 overexpression significantly promoted HepG2 cell proliferation, which was effectively counteracted by VE or γ-T3 treatment in a dose-dependent manner. VE and γ-T3 did not exert their effects through direct regulation of HSD17B4 expression. Instead, γ-T3 was found to interact with HSD17B4, inhibiting its activity in catalyzing the conversion of estradiol (E2) into estrone. Moreover, γ-T3 treatment led to a reduction in cyclin D1 expression and suppressed key proliferation signaling pathways, such as ERK, MEK, AKT, and STAT3. Additionally, γ-T3 promoted apoptosis in HSD17B4-overexpressing HepG2 cells. In an in vivo model, γ-T3 effectively reduced the growth of HepG2 xenograft tumors.Conclusion:In conclusion, our study demonstrates that γ-T3 exhibits potent anti-proliferative and anti-tumor effects against HepG2 cells overexpressing HSD17B4. These findings highlight the therapeutic potential of γ-T3 in HCC treatment and suggest its role in targeting HSD17B4-associated pathways to inhibit tumor growth and enhance apoptosis.

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HSD17B4

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