羟酰辅酶A脱氢酶在癌中作用机制的研究进展

doi:10.16352/j.issn.1001-6325.2024.01.0119

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (1): 119-123.doi: 10.16352/j.issn.1001-6325.2024.01.0119

羟酰辅酶A脱氢酶在癌中作用机制的研究进展

吴国嘏¹, 翟书杰¹, 孙笑¹, 黄怡然¹, 李咏梅¹, 孙丽^2*

1.天津医科大学基础医学院病原生物学系,天津 300211;
2.天津医科大学第二医院妇产科,天津 300070

收稿日期:2023-08-17 修回日期:2023-11-03 出版日期:2024-01-05 发布日期:2023-12-25
通讯作者: ^*:sunl2013@sina.com
基金资助:
天津市教委课题重点项目(2022ZD055);天津医科大学第二医院青年孵育基金(2020ydey13)

Progress of the effect of hydroxyacyl- coenzyme A dehydrogenase in cancer development and its mechanism

WU Guojia¹, ZHAI Shujie¹, SUN Xiao¹, HUANG Yiran¹, LI Yongmei¹, SUN Li^2*

1. Department of Medical Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300211;
2. Department of Gynaecology and Obstetrics, the Second Hospital of Tianjin Medical University, Tianjin 300070, China

Received:2023-08-17 Revised:2023-11-03 Online:2024-01-05 Published:2023-12-25
Contact: ^*:sunl2013@sina.com

摘要/Abstract

摘要： 脂肪酸代谢与癌的发生发展之间存在密切联系。羟酰辅酶 A 脱氢酶(HADH)作为脂肪酸β-氧化的关键酶,近年来被发现在多种癌中为抑癌因子,在急性髓系白血病等中为促癌因子。在癌细胞中,HADH除直接催化脂肪酸β-氧化外,还间接作用于PPAR、TNF-α、JAK-STAT3、PI3K/Akt、IFN-γ、MAPK与非经典Wnt等多种信号通路,影响癌细胞增殖与迁移。HADH作为不同种癌诊断、治疗和预后的潜在肿瘤标志物,具备较高临床应用价值。

关键词: 羟酰辅酶 A 脱氢酶, 脂代谢, 脂肪酸β-氧化, 抑癌基因, 肿瘤标志物

Abstract: A close relationship between fatty acid metabolism and cancer development is well-established. The hydroxyacyl-coenzyme a dehydrogenase (HADH), a key enzyme in fatty acid beta-oxidation, has recently been identified as an anti-oncogenic factor in various cancers and an oncogenic factor in conditions like acute myeloid leukemia. In cancer cells, HADH not only directly catalyzes fatty acid beta-oxidation but also indirectly influences multiple signaling pathways such as PPAR, TNF-α, JAK-STAT3, PI3K/Akt, IFN-γ, MAPK, and non-canonical Wnt signaling pathways, affecting cancer cell proliferation and migration. HADH shows promise as a potential tumor biomarker for diagnosis, treatment, and prognosis in different cancer types, holding significant clinical value.

Key words: hydroxyacyl-coenzyme A dehydrogenase, lipid metabolism, fatty acid β-oxidation, tumor suppressor gene, tumor marker

中图分类号:

吴国嘏, 翟书杰, 孙笑, 黄怡然, 李咏梅, 孙丽. 羟酰辅酶A脱氢酶在癌中作用机制的研究进展[J]. 基础医学与临床, 2024, 44(1): 119-123.

WU Guojia, ZHAI Shujie, SUN Xiao, HUANG Yiran, LI Yongmei, SUN Li. Progress of the effect of hydroxyacyl- coenzyme A dehydrogenase in cancer development and its mechanism[J]. Basic & Clinical Medicine, 2024, 44(1): 119-123.

参考文献 25

[1]	Long W, Wang YB, Qu PF, et al. Functional analysis of HADH c.99C>G shows that the variant causes the proliferation of pancreatic islets and leu-sensitive hyperinsulinaemia[J]. J Genet, 2022, 101:44-51. doi:10.1007/s12041-022-01381-y.
[2]	Ringel AE, Drijvers JM, Baker GJ, et al. Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity[J]. Cell, 2020, 183: 1848-1866. doi:10.1016/j.cell.2020.11.009.
[3]	Alrob OA, Sankaralingam S, Ma C, et al. Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling[J]. Cardiovasc Res, 2014, 103: 485-497. doi:10.1093/cvr/cvu156.
[4]	Yang M, Liu K, Chen P, et al. Bromodomain-containing protein 4 as an epigenetic regulator of fatty acid metabo-lism genes and ferroptosis[J]. Cell Death Dis, 2022, 13: 912-920. doi:10.1038/s41419-022-05344-0.
[5]	Vajravelu ME, Chai J, Krock B, et al. Congenital hyperinsulinism and hypopituitarism attributable to a mutation in FOXA2[J]. J Clin Endocrinol Metab, 2018, 103:1042-1047. doi:10.1210/jc.2017-02157.
[6]	Wilkins OM, Titus AJ, Gui J, et al. Genome-scale identification of microRNA-related SNPs associated with risk of head and neck squamous cell carcinoma[J]. Carcinogenesis, 2017, 38: 986-993. doi:10.1093/carcin/bgx056.
[7]	Shen C, Song YH, Xie Y, et al. Downregulation of HADH promotes gastric cancer progression via Akt signal-ing pathway[J]. Oncotarget, 2017, 8: 76279-76289. doi:10.18632/oncotarget.19348.
[8]	Jiang H, Chen H, Wan P, et al. Decreased expression of HADH is related to poor prognosis and immune infiltration in kidney renal clear cell carcinoma[J]. Genomics, 2021, 113: 3556-3564. doi:10.1016/j.ygeno.2021.08.008.
[9]	Nwosu ZC, Battello N, Rothley M, et al. Correction to: liver cancer cell lines distinctly mimic the metabolic gene expression pattern of the corresponding human tumours. J Exp Clin Cancer Res. 2018,37:267-271. doi:10.1186/s13046-018-0939-4.
[10]	Kim DH, Lee KE. Discovering breast cancer biomarkers candidates through mRNA expression analysis based on the cancer genome atlas database[J]. J Pers Med, 2022, 12:1753-1762. doi:10.3390/jpm12101753.
[11]	Zhang W, Liu B, Wu S, et al. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia[J]. Open Med, 2023, 18: 20220602. doi:10.1515/med-2022-0602.
[12]	Voloshannko O, Schwartz U, Kranz D, et al. β-catenin-independent regulation of Wnt target genes by RoR2 and ATF2/ATF4 in colon cancer cells[J]. Sci Rep, 2018, 8: 3178-3185. doi:10.1038/s41598-018-20641-5.
[13]	Wang R, Li J, Zhou X, et al. Single-cell genomic and transcriptomic landscapes of primary and metastatic colorectal cancer tumors[J]. Genome Med, 2022, 14: 93-101. doi:10.1186/s13073-022-01093-z
[14]	胡晓, 郭然, 张旭光. PPARα缺失加重乙醇诱导的小鼠胃黏膜慢性损伤[J]. 基础医学与临床,2023,43:1505-1511. doi: 10.16352/j.issn.1001-6325.2023.10.1505.
[15]	Zhou X, Fang D, Liu H, et al. PMN-MDSCs accumula-tion induced by CXCL1 promotes CD8 T cells exhaustion in gastric cancer[J]. Cancer Lett, 2022, 532: 215598. doi:10.1016/j.canlet.2022.215598.
[16]	Bakshi HA, Quimn GA, Nasef MM, et al. Crocin inhibits angiogenesis and metastasis in colon cancer via TNF-alpha/NF-kB/VEGF pathways [J]. Cells, 2022, 11:1502-1513. doi:10.3390/cells11091502.
[17]	Leibinger M, Zeitler C, Gobrecht P, et al. Transneuronal delivery of hyper-interleukin-6 enables functional recovery after severe spinal cord injury in mice[J]. Nat Commun, 2021, 12: 391-395. doi:10.1038/s41467-020-20112-4.
[18]	Ham IH, Wang L, Lee D, et al. Curcumin inhibits the cancer-associated fibroblast-derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway[J]. Int J Oncol, 2022, 61:85-93. doi:10.3892/ijo.2022.5375.
[19]	牛世伟, 苏韫, 龚红霞, 等. 胃癌患者血清IL-1的升高和癌组织JAK2/STAT3信号通路的激活[J]. 基础医学与临床, 2022,42:401-405. doi: 10.16352/j.issn.1001-6325.2022.03.035.
[20]	Shiraiwa K, Matsuse M, Nakazawa Y, et al. JAK/STAT3 and NF-kappaB signaling pathways regulate cancer stem-cell properties in anaplastic thyroid cancer cells[J]. Thyroid, 2019, 29: 674-682. doi:10.1089/thy.2018.0212.
[21]	Dunn S, Eberlein C, Yu J, et al. AKT-mTORC1 reactivation is the dominant resistance driver for PI3Kβ/AKT inhibitors in PTEN-null breast cancer and can be over-come by combining with Mcl-1 inhibitors[J]. Oncogene, 2022, 41: 5046-5060.doi:10.1038/s41388-022-02482-9.
[22]	Abdullah ML, Al-shabanah O, Hassan Z K, et al. Eugenol-induced autophagy and apoptosis in breast cancer cells via PI3K/AKT/FOXO3a pathway inhibition[J]. Int J Mol Sci, 2021, 22:9243-9250. doi:10.3390/ijms22179243.
[23]	Sun Y, Zhu L, Liu P, et al. ZDHHC2-mediated AGK palmitoylation activates AKT-mTOR signaling to reduce sunitinib sensitivity in renal cell carcinoma[J]. Cancer Res, 2023, 83: 2034-2051. doi:10.1158/0008-5472.CAN-22-3105.
[24]	Biswas PK, Kwak Y, Kim A, et al. TTYH3 modulates bladder cancer proliferation and metastasis via FGFR1/H-Ras/A-Raf/MEK/ERK pathway[J]. Int J Mol Sci, 2022, 23:10496-10507 doi:10.3390/ijms231810496.
[25]	Chen T, Zhang F, Liu J, et al. Dual role of WNT5A in promoting endothelial differentiation of glioma stem cells and angiogenesis of glioma derived endothelial cells[J]. Oncogene, 2021, 40: 5081-5094. doi:10.1038/s41388-021-01922-2.

羟酰辅酶A脱氢酶在癌中作用机制的研究进展

Progress of the effect of hydroxyacyl- coenzyme A dehydrogenase in cancer development and its mechanism

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