Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"The role of cholesterol biosynthesis and metabolism causing medical complexity in patients with Smith-Lemli-Opitz Syndrome (SLOS)","authors":"Ellen Roy Elias","doi":"10.1016/j.jsbmb.2025.106822","DOIUrl":"10.1016/j.jsbmb.2025.106822","url":null,"abstract":"<div><div>Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive genetic disorder associated with complex anatomic abnormalities, accompanied by medical, developmental and behavioral challenges. It was the first human disorder identified to be caused by an error in the complex cholesterol biosynthetic pathway, more than thirty years ago. This review will cover the clinical and developmental phenotype of patients with SLOS, and the understanding of how cholesterol deficiency, accumulation of the cholesterol precursors 7- and 8-dehydrocholesterol (7-DHC and 8-DHC), and the oxidation of these precursors into toxic oxysterols, are now known to cause this complex phenotype. There is a wide range of severity in patients with SLOS. The most severely affected babies may be miscarried or die in the newborn period due to lethal congenital anomalies. The most mildly impacted patients may show few anatomic abnormalities other than 2–3 toe syndactyly, but still display cognitive and behavioral challenges along the autism spectrum. The review will also cover the medical evaluation and interventions which are recommended in caring for patients with SLOS. There is no cure for this devastating disease, but certain interventions can lead to an improved quality of life, and stabilization of progressive problems for these complex patients.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106822"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of human and rat 17β-hydroxysteroid dehydrogenase 1 by salicylate preservatives: 3D quantitative structure-activity relationship and in silico docking analysis","authors":"Huiqian Zhang ,&nbsp;Jiayi He ,&nbsp;Xiuwei Shen ,&nbsp;Congcong Wen ,&nbsp;Yubin Xu ,&nbsp;Feilu Wang ,&nbsp;Shaowei Wang ,&nbsp;Ren-shan Ge ,&nbsp;Xiaoheng Li","doi":"10.1016/j.jsbmb.2025.106823","DOIUrl":"10.1016/j.jsbmb.2025.106823","url":null,"abstract":"<div><div>The placenta contains 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1), an enzyme critical for converting estrone to estradiol. Salicylates, widely used as preservatives, may inhibit 17β-HSD1, but their inhibitory strength and structure-activity relationships (SAR) remain unclear. This study evaluated 13 structurally diverse salicylates, identifying potent inhibitors of human and rat 17β-HSD1. Menthyl salicylate showed the strongest inhibition in humans (IC₅₀: 5.23 μM) and rats (IC₅₀: 14.85 μM). Inhibition correlated negatively with molecular weight, volume, carbon chain length, and LogP. Mechanistic studies revealed mixed/noncompetitive inhibition in both species. 3D-QSAR and molecular docking highlighted hydrophobic, van der Waals, and hydrogen-bonding interactions at the enzyme’s active site. Key structural features, including carbon chain length and substituent patterns, determined inhibitory potency. These findings clarify SAR and suggest salicylates' potential as endocrine disruptors.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106823"},"PeriodicalIF":2.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mogroside-rich extract alleviates the inflammation state in polycystic ovary syndrome rats through modulating intestinal microbiota-metabolic axis and suppressing the NF-κB/NLRP3 pathway","authors":"Shuai Li ,&nbsp;Renhong Lu ,&nbsp;Benliang Zhou ,&nbsp;Runtian Wan ,&nbsp;Yujun Yan ,&nbsp;Junhan He ,&nbsp;Jiaxin Wu ,&nbsp;Xueping Feng ,&nbsp;Xiaogan Yang ,&nbsp;Xingwei Liang","doi":"10.1016/j.jsbmb.2025.106821","DOIUrl":"10.1016/j.jsbmb.2025.106821","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS), a complex endocrine-metabolic disorder characterized by hyperandrogenism, polycystic ovarian morphology, and ovulatory dysfunction, is often associated with insulin resistance. Mogroside-rich extract (MGE) from <em>Siraitia grosvenorii</em> possesses significant anti-inflammatory and antioxidant properties. However, its potential to restore intestinal microbial homeostasis and metabolic balance in PCOS and the underlying mechanisms remain unexplored. This study investigated MGE's protective effects and mechanisms in a letrozole-induced PCOS rat model. MGE administration significantly ameliorated estrous cycle irregularities, attenuated body weight gain, reduced cystic follicle formation in ovaries, and lowered serum testosterone and insulin levels. Integrated 16S rRNA sequencing and non-targeted metabolomics revealed that MGE enriched beneficial intestinal microbiota (<em>Akkermansia</em>, <em>Parasutterella</em>), associated with anti-inflammatory effects and metabolic improvement, while suppressing pro-inflammatory <em>Corynebacterium</em>. Notably, MGE partially reversed letrozole-induced alterations in colonic metabolites, restoring levels of anti-inflammatory metabolites like butyric acid and gamma-tocotrienol. Furthermore, MGE significantly reduced ovarian pro-inflammatory cytokines and downregulated the expression of p-NF-κB and NLRP3 proteins. Collectively, these findings demonstrate that MGE ameliorates PCOS symptoms by coordinately regulating ovarian inflammation via suppressing the NF-κB/NLRP3 pathway and restoring intestinal microbiota-metabolic axis balance, highlighting its therapeutic potential for PCOS.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106821"},"PeriodicalIF":2.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol acyltransferase-1: A novel diagnostic biomarker and potential therapeutic target for cancer","authors":"Shijie Mao ,&nbsp;Weimin Zhou ,&nbsp;Aiping Cheng ,&nbsp;Hengbin Cao ,&nbsp;Yun Bei","doi":"10.1016/j.jsbmb.2025.106820","DOIUrl":"10.1016/j.jsbmb.2025.106820","url":null,"abstract":"<div><div>Aberrant lipid metabolism, particularly the dysregulation of cholesterol metabolism, is a hallmark of cancer cells, facilitating cancer progression. Targeting intracellular cholesterol homeostasis has emerged as a therapeutic strategy in cancer treatment. Esterification, a critical step for cholesterol storage, mitigates cytotoxicity induced by free cholesterol. Accumulation of cholesterol ester has been extensively revealed as a promoting factor for cancer progression. Elevated expression of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1), the primary enzyme responsible for cholesterol esterification, promotes cancer progression by activating multiple signaling pathways. ACAT-1 has garnered attention as a potential anti-cancer target, with many inhibitors developed and applied in cancer treatment. This review summarizes the effects and potential mechanisms of cholesterol ester accumulation on cancer cell proliferation, invasion, metastasis, chemotherapy resistance and immune evasion. Additionally, the role of ACAT-1 and the application of its inhibitors in various cancers are discussed, offering novel strategies for cancer therapy and diagnosis.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106820"},"PeriodicalIF":2.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of star promoter in common carp and catfish testis: Role of c-jun and its association with testicular function as a transcription factor","authors":"Swathi Tenugu,&nbsp;Balasubramanian Senthilkumaran","doi":"10.1016/j.jsbmb.2025.106817","DOIUrl":"10.1016/j.jsbmb.2025.106817","url":null,"abstract":"<div><div>Steroidogenic acute regulatory protein (Star) is a key factor that predominantly mediates the rate-limiting step of steroidogenesis which involved in the translocation of cholesterol from the outer to inner mitochondrial membrane in most of the vertebrates. To understand the transcriptional regulation of <em>star</em> (<em>star</em>1) in fish, the 5’ upstream region of the <em>star</em> was cloned from both common carp and catfish genomic libraries and <em>in silico</em> promoter motif analysis predicted putative binding sites of C-jun, AP-1, Gata2, and Oct1 in common carp while C-jun, Gata1, Gata2, and Oct1 binding sites were predicted in <em>star</em> promoter of catfish. Luciferase reporter assay through sequential deletion constructs in TM3 cells revealed significantly high promoter activity (P &lt; 0.001) having C-jun site in both common carp and catfish but not with other motifs largely. Increased activity of <em>star</em> promoter was observed upon hCG induction, <em>in vitro</em>, indicating gonadotropin dependency. Site-directed mutagenesis and chromatin immunoprecipitation assays further confirmed the binding of C-jun to the upstream promoter region of <em>star</em> in both species. Expression of <em>c-jun</em> was significantly (P &lt; 0.05) higher during the spawning phase of the testicular cycle in both species. Both <em>c-jun</em> and <em>star</em> were found to be gonadotropin inducible and androgen-dependent in both species. Further, transient gene silencing through <em>c-jun</em>-siRNA in both the species decreased expression of <em>c-jun</em>, <em>star</em>, and other AP-1 factors such as <em>c-fos</em>, <em>junB</em>, <em>sox</em> family genes, steroidogenic enzyme genes, sperm-related factor, testis-related genes, along with reduced testosterone and 11-ketotestosterone levels. The protein level of C-jun was decreased upon transient gene silencing in both species. This was the first report to show that C-jun binds to the upstream promoter motif of <em>stars</em> in both common carp and catfish and also adds valuable new insights that define the molecular mechanisms of <em>c-jun</em> regulating <em>star</em> transcription during steroidogenesis in teleost and probably testicular function.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106817"},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"5α-reductase type 3 is a predictive marker for chemotherapy efficacy in breast cancer in an androgen-independent manner","authors":"Kanoko Nakamura ,&nbsp;Kiyoshi Takagi ,&nbsp;Mio Yamaguchi-Tanaka ,&nbsp;Ai Sato ,&nbsp;Naoki Inoue ,&nbsp;Akiko Ebata ,&nbsp;Yasuhiro Miki ,&nbsp;Minoru Miyashita ,&nbsp;Takashi Suzuki","doi":"10.1016/j.jsbmb.2025.106818","DOIUrl":"10.1016/j.jsbmb.2025.106818","url":null,"abstract":"<div><div>Breast cancer is one of the most representative sex-steroid-dependent cancers and both estrogens and androgens are locally synthesized in breast cancer tissues by sex-steroid producing enzymes. 5<span><math><mi>α</mi></math></span>-reductase (5<span><math><mi>α</mi></math></span>-Red) is an enzyme which reduces testosterone to biologically active dihydrotestosterone (DHT), serving as a regulator of intratumoral DHT levels. To date, three 5<span><math><mi>α</mi></math></span>-Red isozymes have been identified: 5<span><math><mi>α</mi></math></span>-Red types 1–3. However, 5<span><math><mi>α</mi></math></span>-Red type 3 is not fully examined in breast cancer, and its contribution to DHT synthesis is yet to be elucidated. We therefore immunolocalized 5<span><math><mi>α</mi></math></span>-Red type 3 in breast cancer tissues and correlated its immunoreactivity with intratumoral DHT levels as well as clinicopathological parameters. In the present study, 5<span><math><mi>α</mi></math></span>-Red type 3 immunoreactivity was not correlated with intratumoral DHT level. Additionally, the immunoreactivity of 5<span><math><mi>α</mi></math></span>-Red type 3 was negatively correlated with that of 17<span><math><mi>β</mi></math></span>-hydroxysteroid dehydrogenase type 5, which converts androstenedione to testosterone. In the prognostic analysis, although 5<span><math><mi>α</mi></math></span>-Red type 3 immunoreactivity was not correlated with patients’ clinical outcomes in the entire cohort of 172 breast cancer cases, it was significantly correlated with better clinical outcomes in the patients with non-luminal A type breast cancer or in those who received chemotherapy. These findings suggest that 5<span><math><mi>α</mi></math></span>-Red type 3 does not contribute to intratumoral DHT synthesis, while served as a potent predictive marker for efficacy of chemotherapy in breast cancer independent of androgen action.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106818"},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D receptor polymorphisms and their role in invasive breast cancer progression","authors":"Zineb Sakhi ,&nbsp;Mouad Najih ,&nbsp;Khaoula Elghazali ,&nbsp;Kaoutar Anouar Tadlaoui ,&nbsp;Mustapha Benhessou ,&nbsp;Moulay Mustapha Ennaji","doi":"10.1016/j.jsbmb.2025.106819","DOIUrl":"10.1016/j.jsbmb.2025.106819","url":null,"abstract":"<div><div>Vitamin D plays a critical role not only in maintaining bone health and regulating calcium levels, but is also involved in several extra-skeletal functions, including cell physiology, proliferation, differentiation, anti-cancer effects, modulation of immune responses, and inflammation control. Its biological effects are mediated by the nuclear vitamin D receptor (VDR), a member of the steroid hormone receptor family. Genetic variations in this VDR gene, such as the <em>Fok</em>I (rs2228570) and <em>Taq</em>I (rs731236) single nucleotide polymorphisms (SNPs), may alter VDR expression levels, impair protein function, and potentially increase the risk of breast cancer. However, the relationship between these polymorphisms and breast cancer remains controversial. This study aims to assess the association between the <em>Fok</em>I and <em>Taq</em>I polymorphisms of the VDR gene and breast cancer susceptibility in Moroccan women. For this study, breast cancer tissues and control samples were collected, and genomic DNA was extracted. Genotyping of <em>Fok</em>I and <em>Taq</em>I SNPs was performed using TaqMan Real-Time Polymerase Chain Reaction (RT-PCR). Our findings revealed a significant difference in the distribution of <em>Fok</em>I genotypes between breast cancer patients and controls (p = 0.031). The <em>Fok</em>I polymorphism was significantly associated with histoprognostic grade (p &lt; 0.001), tumor stage (p = 0.011), and progesterone receptor (PR) status (p = 0.004), while the <em>Taq</em>I polymorphism showed a significant association with estrogen receptor (ER) status (p = 0.016). These results suggest that the <em>Fok</em>I polymorphism of the VDR gene may influence breast cancer susceptibility. Identifying these genetic variations could provide valuable insights into breast cancer pathogenesis and open avenues for personalized treatment strategies, including the use of VDR agonists as targeted therapies against breast cancer.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106819"},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of lipid metabolism reprogramming and related drug therapy in ovarian cancer","authors":"Xiangyi Li ,&nbsp;Ruibao Guo ,&nbsp;Guang Yang ,&nbsp;Lin Zhu ,&nbsp;Runjiao Liu ,&nbsp;Lei Xia ,&nbsp;Qizhi Zhang","doi":"10.1016/j.jsbmb.2025.106816","DOIUrl":"10.1016/j.jsbmb.2025.106816","url":null,"abstract":"<div><div>Ovarian cancer is the most malignant gynecological tumor. Dysregulation of lipid metabolism is not only associated with the formation of tumor cells, but also plays an important role in the invasion and drug resistance of ovarian cancer. Dysregulation of lipid metabolism involves multiple aspects such as lipid uptake, storage, excretion, and fatty acids oxidation. Dysregulation of lipid metabolism affects tumor proliferation, migration, and drug resistance formation by generating more energy and synthesizing new lipid metabolites or activating related signaling pathways, leading to poor prognosis. This article reviews the role of fatty acid metabolism in ovarian cancer and the research progress in the field of drug therapy, suggesting that fatty acid and related lipid metabolism pathways are potential therapeutic targets for ovarian cancer.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106816"},"PeriodicalIF":2.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-esterified fatty acids disrupt hepatic lipid metabolism and mitochondrial function via TLR4/MyD88/IRAK2 signaling in bovine hepatocytes","authors":"Yongqiang Wen ,&nbsp;Yazhou Wang ,&nbsp;Juan J. Loor ,&nbsp;Chenxu Zhao ,&nbsp;Jianguo Wang","doi":"10.1016/j.jsbmb.2025.106813","DOIUrl":"10.1016/j.jsbmb.2025.106813","url":null,"abstract":"<div><div>Excessive non-esterified fatty acids (NEFA) in the blood often lead to ketosis and fatty liver in peripartal cows. The integrity of mitochondrial structure and function plays a key role in the development of lipid metabolism imbalance and inflammation. However, the precise molecular mechanisms of NEFA's impact on these processes remain unclear. To explore how NEFA (0, 0.3, 0.6, 1.2, and 2.4 mM) influence lipid metabolism, inflammation, and mitochondrial function in perinatal cow hepatocytes. Bovine primary hepatocytes were isolated from five 1-day-old Holstein calves using collagenase IV perfusion, hepatocytes were treated with various concentrations of NEFA for 12 h to systematically simulate the metabolic changes in the negative energy balance (NEB) environment. Oxidative stress levels, lipid metabolism gene and protein expression, inflammatory pathway activation, and mitochondrial structure and function were assessed. Compared with the control group, 1.2 and 2.4 mM NEFA significantly increased lipid accumulation (TAG, T-CHO, LDL-c) and oxidative stress (MDA), while reducing antioxidant levels (GSH, SOD, T-AOC). NEFA upregulated lipogenic genes (SREBP-1c, ACC, FASN) and downregulated lipid oxidation genes (PPARα, CPT1A). Lipid transport was impaired, with altered APOE, LDLR, CD36, and L-FABP expression. NEFA activated the TLR4/MyD88/IRAK2/NF-κB pathway, increasing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Mitochondrial function was impaired, as evidenced by increased ROS, reduced mitochondrial membrane potential, decreased mtDNA levels, and downregulated expression of oxidative phosphorylation genes. NEFA enhanced IRAK2 mitochondrial translocation, inhibited the mitochondrial biogenesis process, and increased apoptosis. NEFA alters lipid metabolism, inflammation, and mitochondrial function in bovine hepatocytes via the TLR4/MyD88/IRAK2 pathway, providing a new target for preventing metabolic diseases in perinatal cows.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106813"},"PeriodicalIF":2.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis reveals the impact of thrombotic diseases on the occurrence and prognosis of breast cancer","authors":"Zhixian Zhong ,&nbsp;Zhiying Wang ,&nbsp;Ting Fan ,&nbsp;Ling Xu ,&nbsp;Qi Li ,&nbsp;Chunyan Dong","doi":"10.1016/j.jsbmb.2025.106815","DOIUrl":"10.1016/j.jsbmb.2025.106815","url":null,"abstract":"<div><div>Venous thromboembolism (VTE) and breast cancer (BC) are two globally prevalent diseases that present significant public health challenges. Despite their impact, the potential genetic association between VTE and BC remains insufficiently investigated. Mendelian randomization (MR) analysis was performed to evaluate the causal influence of VTE on BC. Summary-based Mendelian randomization (SMR) identified BC-induced cis-eQTLs in blood samples, while weighted correlation network analysis (WGCNA) identified VTE-related genes. Colocalization analysis was subsequently conducted to ascertain whether the intersecting genes identified through SMR and WGCNA are implicated in both diseases. MR analysis revealed that VTE conditions, particularly deep vein thrombosis (OR = 1.009, 95 % CI: 1.004–1.014, p = 0.0002) and pulmonary embolism (OR = 1.295, 95 % CI: 1.016–1.650, p = 0.037), may act as risk factors for BC. Colocalization analysis identified three VTE-related genes KCNN4 (PH4 = 0.638), SLC22A5 (PH4 = 0.946), and ZBTB38 (PH4 = 0.945) as being closely associated with BC development. Additionally, ssGSEA analysis demonstrated that both SLC22A5 and KCNN4 were enriched in the IL-17 signaling pathway and exhibited strong correlations with immune cells. Finally, a VTE-related risk score model was constructed, indicating better outcomes in the low-VTE risk score group. This study demonstrated that VTE is closely associated with BC development and identified potential molecular pathways linking the two conditions.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106815"},"PeriodicalIF":2.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}