Scientific Reports
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2025
·Vol. 15
·期 1
·1-12
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IF 3.9
Wu Zhiwei,Zhang Fan,Yang Kai,He Wenfei
Breast cancer is the leading cause of cancer-related death in women worldwide, and its developmental mechanisms involve complex factors. Recent studies have shown that ferroptosis is closely related to the occurrence and progression of breast cancer. However, the role of circular RNAs (circRNAs) in regulating ferroptosis in breast cancer remains unclear. In this study, we investigated the regulatory role of circSCD1 (hsa_circ_0019512) in breast cancer. We examined the expression of circSCD1 in breast cancer cell lines and explored its impact on cell viability and colony formation. We also evaluated the involvement of circSCD1 in ferroptosis by measuring the levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), and intracellular iron. In vivo xenograft experiments were performed to confirm the role of circSCD1 in promoting tumor growth and inhibiting ferroptosis.Furthermore, we investigated the mechanism by which circSCD1 regulates SCD1 protein stability through ubiquitination and identified the interaction between circSCD1 and the deubiquitinase OTUB1. Our results showed that circSCD1 was upregulated in breast cancer cell lines and promoted cell viability and colony formation. Knockdown of circSCD1 increased MDA and ROS levels, decreased GSH levels, and enhanced ferroptosis in breast cancer cells. In vivo, circSCD1 knockdown significantly reduced tumor size and weight, while its overexpression enhanced tumor growth. Mechanistically, circSCD1 interacted with OTUB1 to inhibit the ubiquitination and degradation of SCD1 protein, thereby stabilizing its expression. Rescue experiments demonstrated that SCD1 overexpression partially reversed the effects of circSCD1 knockdown on cell proliferation and ferroptosis. Our findings suggest that circSCD1 plays a crucial role in promoting breast cancer cell growth and inhibiting ferroptosis by regulating SCD1 protein stability. Targeting the circSCD1/OTUB1/SCD1 axis may provide a potential therapeutic strategy for breast cancer treatment.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Adipocyte
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2021
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IF 4.534
Jingwei Zhang,Wei Wang,Ninghan Feng,Xuan Jiang,Shenglong Zhu,Yong Q Chen
Obesity and associated complications are becoming a pandemic. Inhibiting adipogenesis is an important intervention for the treatment of obesity. Despite intensive investigations, numerous mechanistic aspects of adipogenesis remain unclear, and many potential therapeutic targets have yet to be discovered. Transcriptomics and lipidomics approaches were used to explore the functional genes regulating adipogenic differentiation and the potential mechanism in OP9 cells and adipose-derived stem cells. In this study, we found that NADH:ubiquinone oxidoreductase subunit A6 (Ndufa6) participates in the regulation of adipogenic differentiation. Furthermore, we show that the effect of Ndufa6 is mediated through stearoyl-CoA desaturase 1 (Scd1) and demonstrate the inhibitory effect of a SCD1 inhibitor on adipogenesis. Our study broadens the understanding of adipogenic differentiation and offers NDUFA6-SCD1 as a potential therapeutic target for the treatment of obesity.
研究领域:
分子生物学
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细胞生物学
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代谢
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肥胖研究
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DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2025
·Vol. 2025
·期 1
·4955849
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IF 4.2
Zhengrong Chen,Dingwei Yan,Suyu Guo,Yiyi Song,Xinxing Zhang,Wenjing Gu,Heting Dong,Li Huang
Background: This study aimed to explore the mechanisms underlying T-cell differentiation in asthma. Methods and Results: Flow cytometry was performed to detect Th cells. LC-MS/MS was performed to assess lipid metabolism. HE staining was performed to assess the pathological changes of the lung tissues. ELISA was performed to detect cytokine levels. The results of quantitative real-time polymerase chain reaction (qRT-PCR) and western blot showed that miR-192-5p expression was decreased, while SCD1 expression was increased in CD4 + T cells isolated from the peripheral blood of children with asthma. The dual luciferase reporter assay determined the direct interaction between miR-192-5p and SCD1. MiR-192-5p inhibitor reduced ASCL3 and PPARα, increased FASN and SREBP1c mRNA expression and protein levels in mouse spleen CD4 + T cells, and elevated Th2 and Th17 cells, but these effects were reversed by the SCD1 inhibitor. Oleic acid (OA) reduced Th1 cells and increased Th2 and Th17 cells in mouse spleen CD4 + T cells treated with an SCD1 inhibitor. Additionally, pri-miR-192-5p expression was increased in CD4 + T cells isolated from the peripheral blood of asthmatic children, and the deletion of METTL3 upregulated pri-miR-192-5p expression in an m6A-dependent manner. MiR-192-5p mimic and inhibitor both reversed miR-192-5p and SCD1 expression affected by overexpression or deletion of METTL3, both in vivo and in vitro . Furthermore, METTL3 overexpression attenuated lung inflammation, elevated Th1 cells, and reduced Th2 and Th17 cells in CD4 + T cells isolated from the peripheral blood of asthmatic mice. These effects were reversed by the miR-192-5p inhibitor. Conclusion: These results suggest that METTL3/miR-192-5p/SCD1 axis regulates lipid metabolism and affects T cell differentiation, thus affecting asthma progression. This study may provide novel insights into the pathogenesis of asthma and a new treatment strategy.
研究领域:
免疫学
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分子生物学
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呼吸病学
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DOI
PubMed
高影响因子
MOLECULAR THERAPY
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2022
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IF 12.91
Hua-Hua Liu,Yang Xu,Cao-Jie Li,Shu-Jung Hsu,Xia-Hui Lin,Rui Zhang,Jie Chen,Jun Chen,Dong-Mei Gao,Jie-Feng Cui,Xin-Rong Yang,Zheng-Gang Ren,Rong-Xin Chen
Matrix stiffness promotes hepatocellular carcinoma (HCC) metastasis. This study examined the contribution of lipid metabolic reprogramming to matrix stiffness-induced HCC metastasis. HCC cells were cultured on mechanically tunable polyacrylamide gels and subjected to lipidomic analysis. The key enzyme that responded to matrix stiffness and regulated lipid metabolism was identified. The comparative lipidomic screening revealed that stearoyl-CoA desaturase 1 (SCD1) is a mechanoresponsive enzyme that reprogrammed HCC cell lipid metabolism. The genetic and pharmacological inhibition of SCD1 expression/activity altered the cellular lipid composition, which in turn impaired plasma membrane fluidity and inhibited in vitro invasive motility of HCC cells in response to high matrix stiffness. Knockdown of SCD1 suppressed HCC invasion and metastasis in vivo . Conversely, the overexpression of SCD1 or exogenous administration of its product oleic acid augmented plasma membrane fluidity and rescued in vitro invasive migration in HCC cells cultured on soft substrates, mimicking the effects imposed by high matrix stiffness. In human HCC tissues, collagen content, a marker of increasing matrix stiffness, and increased expression of SCD1 together predicted poor survival of HCC patients. An SCD1-dependent mechanoresponsive pathway that responds to increasing matrix stiffness in the tumor microenvironment promotes HCC invasion and metastasis through lipid metabolic reprogramming.
研究领域:
肿瘤学
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分子生物学
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代谢组学
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DOI
PubMed
高影响因子
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
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2022
·Vol. 78
·期 2
·377-388
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IF 5.08
Zhu Shenglong,Zhang Jingwei,Wang Wei,Jiang Xuan,Chen Yong Q.
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with an increasing global prevalence associated with tremendous clinical, economic, and health-related quality-of-life burden. Currently, no effective pharmacological therapy is available for NAFLD. Adipogenesis process is accompanied by fat synthesis which may participate in the occurrence and development of NAFLD. Despite intensive investigations, numerous mechanistic aspects of adipogenesis remain unclear and many potential therapeutic targets are yet to be discovered. In this study, the transcriptomics and lipidomics approaches were used to explore the functional genes regulating adipogenesis and the potential mechanism in OP9 cells and adipose-derived stem cells. We find that NADH:ubiquinone oxidoreductase subunit b9 ( Ndufb9 ) is up-regulated in adipogenesis ( p < 0.001), and silencing Ndufb9 (83% silencing efficiency) inhibits adipogenesis. The effect of Ndufb9 is mediated through stearoyl-CoA desaturase 1 ( Scd1 ). Aramchol, a SCD1 inhibitor, significantly blocks adipogenesis (markedly TG decrease, p < 0.001). Our study broadens the understanding of the role of Ndufb9 in adipogenesis and provides a new target for the treatment of NAFLD.
研究领域:
分子生物学
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细胞生物学
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药理学
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代谢性疾病
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DOI
PubMed
高影响因子
MOLECULAR CANCER RESEARCH
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2022
·Vol. 20
·期 5
·810-822
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IF 6.333
Ding Ming,Zhang Shuwei,Guo Yajuan,Yao Jingjing,Shen Qinghong,Huang Min,Chen Wenbo,Yu Shaofang,Zheng Yaqiu,Lin Yuefang,Yan Wenxin,Liu Zhongqiu,Su Tao,Lu Linlin
Acidification is recognized as the predominant characteristic of the tumor microenvironment (TME) and contributes to tumor progression. However, the mechanism of extracellular acidic TME directly influences intercellular pathologic responses remains unclear. Meanwhile, acidic TME is mainly ascribed to aberrant metabolism of lipids and glucose, but whether and how acidity affects metabolic reprogramming, especially for lipid metabolism, is still unknown. We found that lipid was significantly accumulated in liver cancer cells when exposed to acidic TME. Moreover, proteomic analysis showed that differentially expressed proteins were mainly clustered into fatty acid pathways. Subsequently, we found that acidification increased the expression of SCD1 by activating PI3K/AKT signaling pathway. Interestingly, we found that SCD1 directly bound to PPARα in the acidic TME, which vanished after 2-day reverse incubation in pH 7.4 medium, implying extracellular acidosis might influence intercellular function by mediating the binding affinity between SCD1 and PPARα under different pH gradients. In summary, our data revealed that acidosis could significantly trigger fatty acid synthesis to promote liver tumorigenesis by upregulating SCD1 in a PI3K/AKT activation dependent manner and simultaneously promote SCD1 binding to PPARα. Our study not only provides direct mechanistic evidence to support the vital role of acidosis in lipid metabolic reprogramming, but also provides novel insights for determining the binding affinity of functional proteins as a molecular mechanism to better understand the role of the acidic TME in tumor development. Implications: The acidic TME contributes to lipid accumulation in liver cancer by activating the PI3K/AKT signaling pathway and promoting SCD1–PPARα binding.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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生物化学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2021
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IF 4.932
Hui-Jie Liu,Sheng-Tian Cao,Bao-Ying Wen,Xue Han,Yong Li,Shan Li,Jing Li,Lei Zhang
Non-alcoholic steatohepatitis (NASH) is a devastating form of non-alcoholic fatty liver disease (NAFLD) with distinguished hallmarks of steatosis and inflammation. Rotundic acid (RA) is a natural pentacyclic triterpene compound extracted from the bank of Ilex rotunda Thunb with a wide range of biological activities. The aim of the study is to evaluate the pharmacological effect and action mechanism of RA on NASH in vitro and in vivo . RA has weak lipid lowering ability in rat primary hepatocytes, significantly decreases serum LDL level, hepatic TG and TC levels and lipid droplets, reduces NAS compared with the NASH group, and alleviates hepatic inflammation. RA also enhances the recovery of intestinal bacterial community and intestinal-derived short-chain fatty acid caused by high food diet (HFD). Further investigation shows that RA protects against HFD-induced NASH via downregulating the expression of SREBP-1c/SCD1 signaling pathway and improving gut microbiota. These findings imply that RA might be helpful for the alleviation of NASH.
研究领域:
药理学
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肝病学
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胃肠病学
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微生物学
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DOI
PubMed
高影响因子
Journal of Food Measurement and Characterization
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2024
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IF 2.9
Zeng Xin,Wang Shang,Peng Ze,Wang Meng,Zhao Kui,Xu Ben Bin,Yin Xiongwei,Ibrahim Mohamed M.,Mersal Gaber A. M.,El-Bahy Zeinhom M.,Guo Zhanhu,Xiang Wei,Wang Jianwei
Non-alcoholic fatty liver disease is a prevalent chronic metabolic condition, for which no approved medications are available. As a condiment and traditional Chinese medicine, ginger can be useful in reducing the symptoms of non-alcoholic fatty liver disease. Although its active ingredients and mechanisms of action are unknown, there is a lack of research on them. The purpose of this study is to prepare magnetite (Fe 3 O 4 )@Stearoyl-CoA desaturase 1 (SCD1) materials and analyze them using ultra-high performance liquid-chromatography-mass spectrometry (UPLC-MS) for rapid screening of potential inhibitors of SCD1 in ginger. Based on this analysis, it has been shown that the primary components in ginger that bind SCD1 directly are gingerols, with 10-gingerol having a greater affinity for binding to SCD1 than 8-gingerol and 6-gingerol. Moreover, further studies indicated that free fatty acids (FFA)-induced lipid accumulation is improved by this class of compounds in normal human hepatocytes (THLE-3), with 10-gingerol being the most effective compound. This study provides a new insight into the mechanism, by which ginger contributes to the improvement of non-alcoholic fatty liver disease (NAFLD) and provide support for the effective use of 10-gingerol for the treatment of NAFLD.
研究领域:
药理学
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代谢
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肝病
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天然产物
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药物发现
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产品关联
DOI
高影响因子
Journal of Environmental Sciences
·
2026
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IF 6.5
Xiaoyan Li,Ying Cheng,Zhuling Xu,Runfeng Chang,Jin Yan,Zejun Wang,Xuedong Wang,Huili Wang,Qiuhui Qian
● AgNPs disrupted hepatic lipid metabolism and induced ferroptosis-related toxicity. ● AgNPs induced SCD1 upregulation associated with lipid dysregulation and ferroptosis. ● SCD1 may link lipid metabolism with PPARγ pathway and ferroptosis-related injury. ● AgNPs exposure was associated with insulin resistance– and T2DM-like alterations. Silver nanoparticles (AgNPs) are widely used nanomaterials, yet their potential metabolic and hepatic risks remain insufficiently understood. In this study, we investigated the toxicological effects of AgNPs in zebrafish and explored the potential involvement of a peroxisome proliferator-activated receptor γ (PPARγ)–stearoyl-CoA desaturase 1 (SCD1)–ferroptosis–related pathway associated with lipid metabolic disturbance and type 2 diabetes mellitus (T2DM)-like metabolic alterations. AgNPs exposure induced coordinated upregulation of PPARγ and SCD1 and downregulation of glutathione peroxidase 4 (GPX4), which were accompanied by hepatic lipid accumulation, oxidative stress, and ferroptosis-related responses in larvae, as indicated by elevated reactive oxygen species (ROS) and Fe 2+ levels, glutathione (GSH) depletion, and enhanced lipid peroxidation. These alterations persisted into adulthood and were accompanied by increased body and liver weight, dyslipidemia, hyperglycemia, and impaired insulin signaling, resembling T2DM-like phenotypes. Pharmacological inhibition further supported the involvement of this pathway: the ferroptosis inhibitor deferoxamine (DFO), the PPARγ antagonist 2-chloro-5-nitro-N-(pyridin-4-yl)benzamide (T0070907), and the SCD1 inhibitor 4-(2-chlorophenoxy)-N-[3-[(methylamino)carbonyl]phenyl]-1-piperidinecarboxamide (A939572) significantly alleviated AgNPs-associated hepatic injury. Mechanistic analyses suggest that SCD1, acting downstream of PPARγ, may function as a key mediator linking lipid metabolic dysregulation to ferroptosis. Collectively, these findings provide new insight into the metabolic toxicity associated with AgNPs exposure and contribute to improved ecological and biomedical safety assessment of engineered nanomaterials. Download: Download high-res image (382KB) Download: Download full-size image
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DOI
高影响因子
Journal of Advanced Research
·
2024
·
IF 11.4
Guiqin Huang,Yawen Cai,Menghui Ren,Xiaoyu Zhang,Yu Fu,Run Cheng,Yingdi Wang,Mingxing Miao,Lingpeng Zhu,Tianhua Yan
Introduction Triple-negative breast cancer (TNBC) is the primary cause of breast cancer-induced death in women. Literature has confirmed the benefits of Salidroside (Sal) in treating TNBC. However, the study about potential therapeutic targets and mechanisms of Sal-anchored TNBC remains limited. Objective This study was designed to explore the main targets and potential mechanisms of Sal against TNBC. Methods Network pharmacology, bioinformatics, and machine learning algorithm strategies were integrated to examine the role, potential targets, and mechanisms of the Sal act in TNBC. MDA-MB-231 cells and tumor-bearing nude mice were chosen for in vitro and in vivo experimentation. Cell viability and cytotoxicity were determined using CCK-8, LDH test, and Calcein-AM/PI staining. Antioxidant defense, lipid peroxidation, and iron metabolism were explored using glutathione, glutathione peroxidase, malondialdehyde (MDA), C11-BODIPY 581/591 probe, and FerroOrange dye. Glutathione peroxidase 4 (GPX4) or stearoyl-CoA desaturase 1 (SCD1) overexpression or nuclear receptor co-activator 4 (NCOA4) deficiency was performed to demonstrate the mechanism of Sal on TNBC. Results The prediction results confirmed that 22 ferroptosis-related genes were identified in Sal and TNBC, revealing that the potential mechanism of the Sal act on TNBC was linked with ferroptosis. Besides, these genes were mainly involved in the mTOR, PI3K/AKT, and autophagy signaling pathway by functional enrichment analysis. The in vitro validation results confirmed that Sal inhibited TNBC cell proliferation by modulating ferroptosis via elevation of intracellular Fe 2+ and lipid peroxidation. Mechanistically, Sal sensitized TNBC cells to ferroptosis by inhibiting the PI3K/AKT/mTOR axis, thereby suppressing SCD1-mediated lipogenesis of monounsaturated fatty acids to induce lipid peroxidation, additionally facilitating NCOA4-mediated ferritinophagy to increase intracellular Fe 2+ content. The GPX4 or SCD1 overexpression or NCOA4 deficiency results further supported our mechanistic studies. In vivo experimentation confirmed that Sal is vital for slowing down tumor growth by inducing ferroptosis. Conclusions Overall, this study elucidates TNBC pathogenesis closely linked to ferroptosis and identifies potential biomarkers in TNBC. Meanwhile, the study elucidates that Sal sensitizes TNBC to ferroptosis by SCD1-mediated lipogenesis and NCOA4-mediated ferritinophagy, regulated by PI3K/AKT/mTOR signaling pathways. Our findings provide a theoretical basis for applying Sal to treat TNBC.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
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2026
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IF 10.2
Fan Yu,Shihao Luo,Zhengrong Zhou,Feixia Chen,Jiawei Ying,Qiufang Wu,Yize Wu,Shihua Chen,Xinxin Yao,Feiqin Xie,Wenhui Xu,Ke Xu,Renyi Peng
Cypermethrin (CY), a pyrethroid insecticide, accumulated in aquatic environments and exertd toxic effects on aquatic organisms, impairing their development, nervous system, and immune function. Polystyrene nanoparticles (PS-NPs) readily adsorbed organic contaminants like CY, forming complex pollution systems that resulted in synergistic toxicities. However, the mechanisms behind their hepatotoxicity remained unclear. In this study, both in vivo and in vitro experiments demonstrated that co-exposure to PS-NPs and CY significantly induced liver injury and steatosis in zebrafish larvae, while activating the key lipid synthesis regulator sterol regulatory element-binding protein 1 (SREBP1) in Hep G2 cells. This process displayed typical features of ferroptosis, including oxidative stress, mitochondrial damage, iron dysregulation, and suppression of the antioxidant enzyme glutathione peroxidase 4 (GPX4). Correlation analysis showed a close association between ferroptosis and steatosis. Physiological and genetic verification revealed that Erastin aggravated lipid accumulation by inhibiting GPX4 expression, activating the SREBP1/SCD1 lipid synthesis pathway. Conversely, Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, alleviated oxidative stress, iron overload, and lipid accumulation, while GPX4 overexpression reversed SREBP1/SCD1 activation and improved lipid accumulation, peroxidation, and ferroptosis. This study revealed a novel mechanism by which PS-NPs and CY co-exposure induced ferroptosis-mediated hepatic steatosis through GPX4. These findings provided new insights into the hepatometabolic toxicity of complex pollutants and identified potential targets for preventing related liver diseases.
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产品关联
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PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2024
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IF 4.4
Xuening Ma,Qianchao Shao,Shuxian Huang,Weigao Zhang,Hu Liu,Xu Jiayi,Xunan Zhao,Peiqi Li,Da Shao,YuanQing Bu,Dan Weng
The increasing incidence of cancer underscore the necessity of investigating contributors such as endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA). Although BPA's risks are well-documented, comprehensive studies on its substitutes, such as bisphenol B (BPB), are limited. Dysregulated lipid metabolism is a hallmark of cancer progression. Our previous work demonstrated that BPA and bisphenol S (BPS) disrupt lipid metabolism via the peroxisome proliferator-activated receptor γ (PPARγ) pathway. We hence hypothesized that BPB might similarly perturb lipid metabolism and promote tumor growth. BPB's impact on lipid metabolism was investigated in vitro and in vivo using B16 melanoma cancer cells. Our findings indicate BPB exposure significantly increased lipid metabolism in B16 cells, enhancing cell proliferation and migration, and promoting tumor development in mice. Utilizing siRNA transfection or chemical inhibitor, we found that stearoyl-CoA desaturase-1 (SCD1), a key enzyme in lipid synthesis pathway, was required for BPB-induced lipid accumulation and cancer cell migration. Docking analysis revealed BPB may activate gene expression related to lipid metabolism and angiogenesis by interacting with PPARγ and hypoxia-inducible factor-1α (HIF-1α). This study illuminates BPB's potential role in advancing melanoma through lipid metabolism manipulation, highlighting the need for further research into the safety of BPA substitutes and their impact on cancer development.
研究领域:
肿瘤学
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分子生物学
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环境健康
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）