更新于：2024-09-19

CYP39A1

更新于：2024-09-19

基本信息

别名

24-hydroxycholesterol 7-alpha-hydroxylase、CYP39A1、Cytochrome P450 39A1

+ [5]

简介

A cytochrome P450 monooxygenase involved in neural cholesterol clearance through bile acid synthesis (PubMed:25201972, PubMed:10748047). Catalyzes 7-alpha hydroxylation of (24S)-hydroxycholesterol, a neural oxysterol that is metabolized to bile acids in the liver (PubMed:25201972, PubMed:10748047). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:25201972, PubMed:10748047).

关联

100 项与 CYP39A1 相关的临床结果

登录后查看更多信息

100 项与 CYP39A1 相关的转化医学

登录后查看更多信息

0 项与 CYP39A1 相关的专利（医药）

登录后查看更多信息

项与 CYP39A1 相关的文献（医药）

2024-03-01·Molecular Genetics and Metabolism Reports

Cytochrome P450 genes expression in human prostate cancer

Article

作者: Tymoshenko, Andriy ; Gerashchenko, Ganna ; Stakhovsky, Eduard ; Rosohatska, Inna ; Maksymchuk, Oksana ; Kashuba, Volodymyr ; Kononenko, Oleksiy

CYP-dependent metabolites play a critical role in regulating the cell cycle, as well as the proliferative, invasive, and migratory activity of cancer cells. We conducted a study to analyze the relative gene expression of various CYPs (CYP7B1, CYP27A1, CYP39A1, CYP51, CYP1B1, CYP3A5, CYP4F8, CYP5A1, CYP4F2, CYP2J2, CYP2E1, CYP2R1, CYP27B1, CYP24A1) in 41 pairs of prostate samples (tumor and conventional normal tissues) using qPCR. Our analysis determined significant individual variability in the expression levels of all studied CYPs, both in the tumor and in conventionally normal groups. However, when we performed a paired test between the tumor and normal groups, we found no significant difference in the expression of the studied genes. We did observe a tendency to increase the level of CYP1B1 expression in the tumor group. We also did not find any significant difference between the levels of the studied CYPs in the tumor and conventional normal groups at different stages of prostate cancer and pathomorphological indicators. Correlation analysis revealed the presence of a positive relationship between the expressions of some cholesterol-metabolizing CYP genes, as well as between genes responsible for vitamin D biosynthesis and cholesterol biosynthesis. We observed significant correlative relationships between the expression of CYPs and some prostate cancer-related genes (CDH2, MMP9, SCHLAP1, GCR, CYP17A1, ACTA2, CXCL14, FAP, CCL17, MSMB, IRF1, VDR). Therefore, the expression of CYPs is not directly associated with prostate cancer but is largely determined by genetic, epigenetic factors, as well as endogenous substrates and xenobiotics. The significant correlative relationship between CYPs and genes associated with cancer may indicate common regulatory pathways that may have a synergistic effect on the tumor, ensuring the survival of cancer cells.

2023-11-01·Pathology - Research and Practice

Expression of an oxysterol-metabolizing enzyme in colorectal cancer and its relation to tumor cell behavior and prognosis

Article

作者: Joo, Young-Eun ; Park, Sun-Young ; Park, Young-Lan ; Kim, Ki-Hyun

Oxysterols and oxysterol-metabolizing enzymes have been implicated in the pathogenesis of various cancers. However, the distinct function of the oxysterol-metabolizing enzyme cytochrome P450 family 39 Subfamily A Member 1 (CYP39A1) in colorectal cancer (CRC) remains unclear. The aims of the current study were to evaluate whether CYP39A1 affects the oncogenic behaviors of CRC cells and to investigate the prognostic value of its expression in CRC. A CYP39A1 small-interfering RNA was used to block CYP39A1 gene expression in DLD1 and SW480 cells. The expression of CYP39A1 in CRC tissues was investigated by immunohistochemistry. Tumor angiogenesis and lymphangiogenesis were assessed by CD34 and D2-40 immunohistochemical staining, respectively. CYP39A1 knockdown inhibited tumor cell migration and invasion in DLD1 and SW480 cells. Angiogenesis was also inhibited through the decreased expression of vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor (HIF)-1α, and angiostatin and endostatin expression increased. In addition, CYP39A1 knockdown inhibited the lymphangiogenesis by decreasing the expression of VEGF-C. CYP39A1 expression was increased in CRC tissues compared with normal colorectal mucosa. CYP39A1 expression was associated with tumor stage, depth of invasion, lymph node metastasis, distant metastasis, and poor survival. The microvessel and lymphatic vessel density values of CYP39A1-positive tumors were significantly higher than those of CYP39A1-negative tumors. These results indicate that CYP39A1 is associated with tumor progression by influencing tumor cell angiogenesis and lymphangiogenesis in CRC.

2023-05-30·International journal of molecular sciences

The Placenta-A New Source of Bile Acids during Healthy Pregnancy? First Results of a Gene Expression Study in Humans and Mice.

Article

作者: Ok, Linda ; Ontsouka, Edgar ; Albrecht, Christiane ; Schroeder, Mariana ; Stroka, Deborah ; Vaillancourt, Cathy

Bile acids (BAs) are natural ligands for several receptors modulating cell activities. BAs are synthesized via the classic (neutral) and alternative (acidic) pathways. The classic pathway is initiated by CYP7A1/Cyp7a1, converting cholesterol to 7α-hydroxycholesterol, while the alternative pathway starts with hydroxylation of the cholesterol side chain, producing an oxysterol. In addition to originating from the liver, BAs are reported to be synthesized in the brain. We aimed at determining if the placenta potentially represents an extrahepatic source of BAs. Therefore, the mRNAs coding for selected enzymes involved in the hepatic BA synthesis machinery were screened in human term and CD1 mouse late gestation placentas from healthy pregnancies. Additionally, data from murine placenta and brain tissue were compared to determine whether the BA synthetic machinery is comparable in these organs. We found that CYP7A1, CYP46A1, and BAAT mRNAs are lacking in the human placenta, while corresponding homologs were detected in the murine placenta. Conversely, Cyp8b1 and Hsd17b1 mRNAs were undetected in the murine placenta, but these enzymes were found in the human placenta. CYP39A1/Cyp39a1 and cholesterol 25-hydroxylase (CH25H/Ch25h) mRNA expression were detected in the placentas of both species. When comparing murine placentas and brains, Cyp8b1 and Hsd17b1 mRNAs were only detected in the brain. We conclude that BA synthesis-related genes are placentally expressed in a species-specific manner. The potential placentally synthesized BAs could serve as endocrine and autocrine stimuli, which may play a role in fetoplacental growth and adaptation.

项与 CYP39A1 相关的新闻（医药）

2023-12-28

·今日头条

新线索！海军军医大学发现肝细胞癌性别差异机制

本文为转化医学网原创，转载请注明出处作者：Rainbow 导读：性别差异在肝细胞癌（HCC）中构成了一个重要问题。然而，HCC中性别二态性的机制仍未完全理解。 12月26日，海军军医大学刘辉、杨富共同通讯在期刊《CLINICAL AND TRANSLATIONAL MEDICINE》上在线发表题为“Gender dimorphism in hepatocarcinogenesis—DNA methylation modification regulated X-chromosome inactivation escape molecule XIST”的研究论文，研究结果表明，由YY1-TET2复合物调控的XIST表达水平与女性肝细胞癌（HCC）患者的预后相关。结果显示，XIST可能在女性肝癌发生中起到肿瘤抑制基因的作用。对XCI调控网络的更好理解可能有助于为女性肝癌的临床治疗开发相关的靶向治疗方法。这项研究为研究肝癌发生中的性别差异提供了新的线索。 https://onlinelibrary.wiley.com/doi/10.1002/ctm2.1518 研究背景 01 原发性肝癌发病率很高，并且具有极高的致死率，对人类健康构成了巨大威胁。它在男性中比在女性中更为常见。男性肝癌的发病率和死亡率分别为每10万人口14.1和12.9，而女性的发病率和死亡率分别为每10万人口5.2和4.8。在过去的几十年里，研究人员认为性激素是肝细胞癌性别差异的关键。雌激素通过miRNA、DNA修复和与肥胖相关的途径抑制肝癌的发展和进展。相反，雄激素和雄激素受体起促进作用。此外，具有女性优势表达的常染色体基因CYP39A1是肝癌发展的强力抑制因子，为肝癌性别差异提供了可能的机制。一些逃逸X染色体失活（XCI）的转录本也导致了肝癌的性别差异，例如FTX、JPX和XIST。XIST是位于X染色体失活中的lncRNA，是X染色体失活的重要介质。证据表明，XIST在性别差异性疾病，如自身免疫性疾病、性别差异性癌症、神经系统疾病等中发挥了重要的调节作用。然而，分子机制仍需深入探讨。早期研究发现，许多癌症普遍存在DNA低甲基化的趋势。性别特异的甲基化模式在肝脏中也非常广泛。DNA甲基化是伴随着DNA去甲基化的动态过程。5-甲基胞嘧啶（5mC）可以逐渐被Tet甲基胞嘧啶双氧化酶（TET）酶（TET1、TET2和TET3）氧化为5-羟甲基胞嘧啶（5hmC）。由于5mC和5hmC在人类基因组中的广泛分布、化学稳定性较高以及与基因表达的密切相关，一些学者提出5mC和5hmC可以作为癌症诊断的理想生物标志物。研究发现 02 在这项研究中，研究人员首先使用5hmC-Seal技术检测了四名女性和四名男性肝细胞癌患者的5hmC分布是否存在性别差异。结果表明，女性和男性肝细胞癌患者的5hmC分布存在显著差异。女性HCC组织中XIST第一外显子的5hmC读数明显低于邻近正常肝组织。接着，研究人员阐明了XIST对女性HCC肿瘤抑制功能的调节机制。研究提供了对肝细胞癌性别差异机制的新线索。女性肝细胞癌（HCC）组织中 XIST第一外显子的甲基化水平较高 03 研究人员用Shiny甲基化分析资源工具(SMART,http://www.bioinfo-zs.com/smartapp/)在HCC样本中检查了DNA甲基化水平与XIST之间的关联。研究人员选择位于XIST第一外显子区域的探针（cg:05533223、cg:03554089和cg:12653510）进行数据分析。在女性HCC组织中，XIST表达与甲基化呈极强的负相关。在男性HCC组织中，XIST表达与探针cg:12653510的甲基化呈显著负相关。然而，在男性HCC组织中，另两个探针的甲基化与XIST表达之间没有相关性。研究人员使用Sequenom MassARRAY甲基化分析技术检测了XIST第一外显子区域的甲基化水平。为检测XIST第一外显子区域，设计了检测引物（探针cg05533223也位于目标序列中），用于检测九名女性HCC患者和十名男性HCC患者。在该区域分析了十二个CpG位点。研究人员对XIST第一外显子区域的CpG位点甲基化水平进行了定量分析，并进行了T组和L组的比较。对于女性患者，T组中所有CpG位点的甲基化水平明显高于L组。相反，在男性HCC患者中并未观察到显著变化。研究结果 04 综上所述，研究结果表明，由YY1-TET2复合物调控的XIST表达水平与女性肝细胞癌（HCC）患者的预后相关。结果显示，XIST可能在女性肝癌发生中起到肿瘤抑制基因的作用。对XCI调控网络的更好理解可能有助于为女性肝癌的临床治疗开发相关的靶向治疗方法。这项研究为研究肝癌发生中的性别差异提供了新的线索。参考资料： https://onlinelibrary.wiley.com/doi/10.1002/ctm2.1518 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 北京｜12月19日-20日 ▶第四届单细胞测序技术应用研讨会暨单细胞&空间组学研讨会（日程稍后公布）点击对应文字查看详情

临床结果临床研究