Molecular omics最新文献

筛选
英文 中文
MOFNet: a deep learning framework for multi-omics data fusion in cancer subtype classification MOFNet:用于癌症亚型分类中多组学数据融合的深度学习框架。
IF 2.4 4区 生物学
Molecular omics Pub Date : 2025-10-01 DOI: 10.1039/D5MO00221D
Guangji Zhang, Chunxiao Zhang, Pengpai Li, Duanchen Sun, Zhixia Yang and Zhi-Ping Liu
{"title":"MOFNet: a deep learning framework for multi-omics data fusion in cancer subtype classification","authors":"Guangji Zhang, Chunxiao Zhang, Pengpai Li, Duanchen Sun, Zhixia Yang and Zhi-Ping Liu","doi":"10.1039/D5MO00221D","DOIUrl":"10.1039/D5MO00221D","url":null,"abstract":"<p >Background: cancer exhibits high molecular and clinical heterogeneity, making accurate subtyping essential for personalized treatment. Traditional single-omics approaches often fail to capture this complexity. Multi-omics integration offers a more holistic understanding, but many existing methods either lack interpretability or fail to model cross-omics correlations effectively. Methods: we developed MOFNet, a novel supervised deep learning framework for multi-omics integration, incorporating a similarity graph pooling (SGO) module and a view correlation discovery network (VCDN). MOFNet processes omics data—including mRNA expression, DNA methylation, and miRNA expression—<em>via</em> omics-specific graph learning and cross-omics label space fusion. Three cancer types—breast cancer (BRCA), low-grade glioma (LGG), and stomach adenocarcinoma (STAD)—were analyzed using datasets from the cancer genome atlas (TCGA). Statistical evaluation was performed using accuracy, weighted F1 score, and macro F1 score across stratified training/testing splits. Results: MOFNet achieved superior performance across all datasets. For BRCA, it obtained an accuracy of 85.17%, F1_weighted of 85.36%, and macro F1 of 80.93%, outperforming all baseline models by up to 18.25%. In LGG and STAD, MOFNet also showed robust gains, with maximum improvements of 23.72% and 21.56%, respectively. Omics ablation studies demonstrated enhanced performance with multi-omics integration. Functional enrichment analysis revealed that MOFNet-identified key features were involved in biologically relevant pathways such as cell cycle regulation, synaptic signaling, and ion transport. Conclusions: MOFNet enables scalable and interpretable multi-omics data fusion for cancer subtype classification, significantly improving predictive accuracy while retaining only 25% of input features. The integration of SGO and VCDN modules offers both biological interpretability and computational efficiency. These results suggest MOFNet's promising application in precision oncology and biomarker discovery.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 690-705"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MALDI mass spectrometry imaging in plant and food lipidomics: advances, challenges, and future perspectives MALDI质谱成像在植物和食品脂组学:进展,挑战和未来展望。
IF 2.4 4区 生物学
Molecular omics Pub Date : 2025-09-26 DOI: 10.1039/D5MO00116A
G. Ventura, M. Bianco, I. Losito, T. R. I. Cataldi and C. D. Calvano
{"title":"MALDI mass spectrometry imaging in plant and food lipidomics: advances, challenges, and future perspectives","authors":"G. Ventura, M. Bianco, I. Losito, T. R. I. Cataldi and C. D. Calvano","doi":"10.1039/D5MO00116A","DOIUrl":"10.1039/D5MO00116A","url":null,"abstract":"<p >Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has established itself as a powerful analytical technique for spatially resolved lipidomics, offering unique insights into lipid distribution and metabolism directly within plant and food matrices. Recent methodological and technological advances have markedly improved the spatial resolution, sensitivity, and selectivity of MALDI-MSI, enabling high-definition mapping of complex lipidomes down to the cellular level. This review presents the current state of MALDI-MSI applications in plant and food lipidomics, with a focus on studies that have advanced our understanding of lipid heterogeneity, metabolic pathways, and spatial lipid organization. Special attention is given to the analytical challenges associated with lipid structural diversity, particularly isomerism and isobarism, and to the strategies developed to address these limitations. Emerging applications involving stable isotope labelling, advanced ion mobility spectrometry, and chemical derivatization are also discussed, highlighting their potential to enhance lipid identification and spatial localization. Finally, the review outlines future perspectives, emphasizing the integration of MALDI-MSI with complementary omics approaches and advanced computational tools to accelerate discoveries in plant biology, food quality assessment, and nutritional science.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 566-581"},"PeriodicalIF":2.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Network-driven identification of indisulam neo-substrates for targeted protein degradation 针对蛋白降解的胰岛素新底物的网络驱动鉴定。
IF 2.4 4区 生物学
Molecular omics Pub Date : 2025-09-23 DOI: 10.1039/D5MO00053J
Andrew F. Jarnuczak, Orli Yogev, Angelo Andres, Stephanie K. Ashenden, Cheng Ye, Fiona Pachl, Andrew Zhang, Maria Emanuela Cuomo and Meizhong Jin
{"title":"Network-driven identification of indisulam neo-substrates for targeted protein degradation","authors":"Andrew F. Jarnuczak, Orli Yogev, Angelo Andres, Stephanie K. Ashenden, Cheng Ye, Fiona Pachl, Andrew Zhang, Maria Emanuela Cuomo and Meizhong Jin","doi":"10.1039/D5MO00053J","DOIUrl":"10.1039/D5MO00053J","url":null,"abstract":"<p >Indisulam, a DCAF15-based molecular glue degrader, induces widespread proteome changes with implications for cell division and chromosome segregation. While RBM39 and RBM23 are two well-characterized indisulam neo-substrates, additional targets likely exist. To identify those degradation targets, we applied a network-based approach to prioritize novel neo-substrates from large-scale omics data. Our approach integrates proteome-wide expression measurements with information from publicly accessible databases into a multilayer heterogeneous network. Utilizing a Random Walk with Restart algorithm, we identified a preliminary list of 30 neo-substrates. These proteins are likely interactors with DCAF15 in the presence of indisulam and are subject to subsequent degradation. Experimental validation of hits from the shortlisted candidates confirmed their degradation in a proteasome-dependent manner, supporting their identification as potential novel indisulam neo-substrates. Our work employs established network resources and analytical methods to effectively identify direct targets of the indisulam molecular glue degrader. This approach is readily adaptable for exploring novel targets across other molecular glue systems, enhancing its applicability and value to the drug discovery community.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 668-677"},"PeriodicalIF":2.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prunus mongolica oil attenuates hepatic fibrosis via a lncRNA-mediated ceRNA network targeting dual PGC-1α/PPARγ and TGF-β/Smad3 pathways 蒙古李油通过lncrna介导的ceRNA网络靶向PGC-1α/PPARγ和TGF-β/Smad3双通路减轻肝纤维化。
IF 2.4 4区 生物学
Molecular omics Pub Date : 2025-09-23 DOI: 10.1039/D5MO00083A
YiJie Hou, HongBing Zhou, XiaoGang Li, JiaXing Gao, Hong Chang, Jia Wang, YingChun Bai, ShuYuan Jiang, ShuFang Niu, WanFu Bai and SongLi Shi
{"title":"Prunus mongolica oil attenuates hepatic fibrosis via a lncRNA-mediated ceRNA network targeting dual PGC-1α/PPARγ and TGF-β/Smad3 pathways","authors":"YiJie Hou, HongBing Zhou, XiaoGang Li, JiaXing Gao, Hong Chang, Jia Wang, YingChun Bai, ShuYuan Jiang, ShuFang Niu, WanFu Bai and SongLi Shi","doi":"10.1039/D5MO00083A","DOIUrl":"10.1039/D5MO00083A","url":null,"abstract":"<p >Hepatic fibrosis (HF), a reversible yet critical pathological stage in chronic liver disease progression, represents a major global public health challenge. This study systematically investigated the antifibrotic mechanism of <em>Prunus mongolica</em> oil (OIL), an active component derived from traditional medicinal plants, through an integrated approach combining pharmacodynamics, transcriptomics, and molecular biology in carbon tetrachloride (CCl<small><sub>4</sub></small>)-induced Sprague–Dawley rat models. Dose–response evaluation revealed optimal antifibrotic efficacy at the medium dosage (5 g kg<small><sup>−1</sup></small>) compared with other concentrations (2.5 and 7.5 g kg<small><sup>−1</sup></small>). Transcriptomic profiling identified 1734 differentially expressed mRNAs, 121 lncRNAs, and 82 miRNAs among model (MOD), control (CON), and OIL-treated groups. Construction of competing endogenous RNA (ceRNA) networks and functional enrichment analysis highlighted the potential association of the PPAR signaling pathway (<em>P</em> = 0.012, FDR = 0.27). Topological assessment using Cytoscape (v3.9.1) and the STRING database identified the Gck/rno-miR-667-5p/Cyp8b1 axis as the central regulatory node. Mechanistically, OIL exerted dual therapeutic effects: (1) upregulating PGC-1α/PPARγ expression to enhance metabolic reprogramming, and (2) suppressing TGF-β/Smad3 phosphorylation activation, thereby inhibiting hepatic stellate cell (HSC) activation and extracellular matrix (ECM) deposition. Immunohistochemical and western blot analyses validated these protein-level modulations. Our findings revealed a novel ceRNA-network-mediated mechanism wherein OIL attenuates hepatic fibrosis through coordinated regulation of PPAR and TGF-β/Smad3 pathways <em>via</em> the Gck/rno-miR-667-5p/Cyp8b1 axis, providing a theoretical foundation for developing multitarget phytopharmaceuticals against liver fibrosis.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 657-667"},"PeriodicalIF":2.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mammary gland metabolism and its relevance to the fetoplacental expression of cytokine signaling in caveolin-1 null mice 小窝蛋白-1缺失小鼠乳腺代谢及其与胎胎盘细胞因子信号表达的相关性
IF 2.4 4区 生物学
Molecular omics Pub Date : 2025-09-10 DOI: 10.1039/D5MO00059A
Shankar P. Poudel, Maliha Islam, Thomas B. McFadden and Susanta K. Behura
{"title":"Mammary gland metabolism and its relevance to the fetoplacental expression of cytokine signaling in caveolin-1 null mice","authors":"Shankar P. Poudel, Maliha Islam, Thomas B. McFadden and Susanta K. Behura","doi":"10.1039/D5MO00059A","DOIUrl":"10.1039/D5MO00059A","url":null,"abstract":"<p >Mice lacking caveolin-1 (<em>Cav1</em>), a major protein of the lipid raft of plasma membrane, show deregulated cellular proliferation of the mammary gland and an abnormal fetoplacental communication during pregnancy. This study leverages a multi-omics approach to test the hypothesis that the absence of <em>Cav1</em> elicits a coordinated crosstalk of genes among the mammary gland, placenta and fetal brain in pregnant mice. Integrative analysis of metabolomics and transcriptomics data of mammary glands showed that the loss of <em>Cav1</em> significantly impacted specific metabolites and metabolic pathways in the pregnant mice. Next, gene expression changes of the deregulated metabolic pathways of the mammary gland were compared with the gene expression changes of the placenta and fetus. The analysis showed that genes associated with specific metabolic and signaling pathways changed in a coordinated manner in the placenta, mammary gland and fetal brain of <em>Cav1</em>-null mice. The cytokine signaling pathway emerged as a key player of the molecular crosstalk among these tissues. By interrogating the single-nuclei gene expression data of placenta and fetal brain previously generated from <em>Cav1</em>-null mice, the study further revealed that these metabolic and signaling genes were differentially regulated in specific cell types of the placenta and fetal brain. Though a causal effect of the mammary gland on the placenta and/or fetal brain can’t be inferred from this study, the findings show that the mammary gland, placenta and fetal brain show a coordinated molecular crosstalk in response to the absence of <em>Cav1</em> in mice.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 5","pages":" 512-523"},"PeriodicalIF":2.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep learning methods and applications in single-cell multimodal data integration 深度学习方法及其在单细胞多模态数据集成中的应用。
IF 2.4 4区 生物学
Molecular omics Pub Date : 2025-09-10 DOI: 10.1039/D5MO00062A
Franklin Vinny Medina Nunes, Luiza Marques Prates Behrens, Rafael Diogo Weimer, Gabriela Flores Gonçalves, Guilherme da Silva Fernandes and Márcio Dorn
{"title":"Deep learning methods and applications in single-cell multimodal data integration","authors":"Franklin Vinny Medina Nunes, Luiza Marques Prates Behrens, Rafael Diogo Weimer, Gabriela Flores Gonçalves, Guilherme da Silva Fernandes and Márcio Dorn","doi":"10.1039/D5MO00062A","DOIUrl":"10.1039/D5MO00062A","url":null,"abstract":"<p >The integration of multimodal single-cell omics data is a state-of-art strategy for deciphering cellular heterogeneity and gene regulatory mechanisms. Recent advances in single-cell technologies have enabled the comprehensive characterization of cellular states and their interactions. However, integrating these high-dimensional and heterogeneous datasets poses significant computational challenges, including batch effects, sparsity, and modality alignment. Deep learning has shown great promise in addressing these issues through neural network-based frameworks, including variational autoencoders (VAEs) and graph neural networks (GNNs). In this Review, we examine cutting-edge deep learning methodologies for integrating single-cell multimodal data, discussing their architectures, applications, and limitations. We highlight key tools such as sciCAN, scJoint, and scMaui, which use deep learning techniques to harmonize various omics layers, improve feature extraction, and improve downstream biological analyses. Despite significant advancements, it remains challenging to ensure model interpretability, scalability, and generalizability across different datasets. Future directions of research in this field include the development of self-supervised learning strategies, transformer-based architectures, and federated learning frameworks to enhance the robustness and reproducibility of single-cell multi-omics integration.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 545-565"},"PeriodicalIF":2.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Differentially regulated saliva proteome and metabolome: a way forward for risk-assessment of oral cancer among tobacco abusers† 差异调节唾液蛋白质组和代谢组:烟草滥用者口腔癌风险评估的前进方向。
IF 2.4 4区 生物学
Molecular omics Pub Date : 2025-09-03 DOI: 10.1039/D5MO00058K
Bolaji Fatai Oyeyemi, Shruti Dabral, Amit Paramaraj, Sandhya Srinivasan, Gagan Deep Jhingan, Dhiraj Kumar, Chintamani, Abhinav Kumar and Néel Sarovar Bhavesh
{"title":"Differentially regulated saliva proteome and metabolome: a way forward for risk-assessment of oral cancer among tobacco abusers†","authors":"Bolaji Fatai Oyeyemi, Shruti Dabral, Amit Paramaraj, Sandhya Srinivasan, Gagan Deep Jhingan, Dhiraj Kumar, Chintamani, Abhinav Kumar and Néel Sarovar Bhavesh","doi":"10.1039/D5MO00058K","DOIUrl":"10.1039/D5MO00058K","url":null,"abstract":"<p >Oral cancer (OC) is a malignant tumour with high morbidity and mortality. Significant contributory factors include alcohol and tobacco abuse that dysregulate the proteome and metabolome. We assessed saliva as a noninvasive bio-sample to understand the changes in proteome and metabolome in OC, tobacco abusers (TA), and controls. OC, TA, and control samples (<em>n</em> = 22, 21, and 21, respectively) were subjected to LFQ-proteomics and NMR-based metabolomics analyses individually and integrated using systems biology; 292 out of 758 proteins with two or more unique peptides were significantly differently regulated. Functional annotation revealed that differentially expressed proteins are involved in important cellular metabolic processes. PLS-DA in metabolomics separated OC from the control and TA, and <em>K</em>-means clustering of proteomics and metabolomics profiles revealed distinguishing proteins and metabolites in OC, TA, and the control. Integrated analysis revealed convergence on molecules like transketolase (TKTT), transaldolase (TALDO), kallikrein 1 (KLK1), enolase A (ENOA), glucose-6-phosphate isomerase (G6PI), and aldolase A and C (ALDOA and ALDOC). Finally, the characteristic discriminatory features of several clusters between OC, TA, and the control remain valid only among high tobacco abusers. The results reveal metabolites that could serve as early indicators for OC, especially among chewing tobacco abusers, and therefore establish the basis for larger cohort studies to develop them as predictive OC biomarkers.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 594-606"},"PeriodicalIF":2.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative glycomic analysis of hawk (Rupornis magnirostris), caiman (Caiman latirostris) and sea turtle (Caretta caretta) tear films 鹰(Rupornis magnirostris)、凯门鳄(caiman latirostris)和海龟(Caretta Caretta)泪膜的比较糖谱分析。
IF 2.4 4区 生物学
Molecular omics Pub Date : 2025-09-02 DOI: 10.1039/D4MO00255E
Ana Cláudia Raposo, Sheryl Joyce B. Grijaldo-Alvarez, Gege Xu, Michael Russelle S. Alvarez, Carlito B. Lebrilla, Ricardo Wagner Portela and Arianne Oriá
{"title":"Comparative glycomic analysis of hawk (Rupornis magnirostris), caiman (Caiman latirostris) and sea turtle (Caretta caretta) tear films","authors":"Ana Cláudia Raposo, Sheryl Joyce B. Grijaldo-Alvarez, Gege Xu, Michael Russelle S. Alvarez, Carlito B. Lebrilla, Ricardo Wagner Portela and Arianne Oriá","doi":"10.1039/D4MO00255E","DOIUrl":"10.1039/D4MO00255E","url":null,"abstract":"<p >Glycans are recognized as biomarkers and therapeutic targets. However, these molecules remain a critical blind spot in understanding post-translational modifications, particularly in vertebrate species inhabiting diverse habitats. The glycans present in tears play a crucial role in eye protection and may be one of the key factors in adapting to direct environmental contact. This study aimed to describe and compare the glycomic profiles of roadside hawk (<em>Rupornis magnirostris</em>), broad-snouted caiman (<em>Caiman latirostris</em>), and loggerhead sea turtle (<em>Caretta caretta</em>) tears, thereby one avian and two reptilian species. Samples were collected from 10 healthy roadside hawks, 70 broad-snouted caimans, and 10 loggerhead sea turtles to determine <em>N</em>- and <em>O</em>-glycan compounds. The compounds were released from tear glycoproteins and enriched by solid-phase extraction (SPE). Then, the glycans were eluted based on size and polarity. SPE fractions were analyzed using high-resolution mass spectrometry. 155 <em>N</em>-glycans (56% sialylated) and 259 <em>O</em>-glycans (37% sialylated) were detected in roadside hawk tears; 127 <em>N</em>-glycans (55% sialylated) and 263 <em>O</em>-glycans (35% sialofucosylated) in broad-snouted caiman tears; and 85 <em>N</em>-glycans (36% fucosylated) and 84 <em>O</em>-glycans (89% fucosylated) in loggerhead sea turtle tears. The marine habitat has a significant impact on the tear's glycans. The high presence of fucosylated glycans can represent a shield mechanism potentially related to its adhesion to glycocalyx, and interaction with the immune system, also serving as an environmental biomarker. Tears are composed of various biologically active substances, and this description can help in further studies on the identification of novel ocular surface biomarkers and in the differentiation of glycan profiles in healthy and non-healthy animals.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 633-644"},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thioridazine induces phospholipid accumulation and necroptosis in parental and tamoxifen-resistant breast cancer cells† 硫吡嗪诱导亲代和他莫昔芬耐药乳腺癌细胞的磷脂积累和坏死下垂。
IF 2.4 4区 生物学
Molecular omics Pub Date : 2025-07-28 DOI: 10.1039/D5MO00039D
Chandrasekaran Mythri, Sachin B Jorvekar, Nirawane Suraj, Nethaji Pruthiviraj, Roshan M Borkar and Sudhagar Selvaraju
{"title":"Thioridazine induces phospholipid accumulation and necroptosis in parental and tamoxifen-resistant breast cancer cells†","authors":"Chandrasekaran Mythri, Sachin B Jorvekar, Nirawane Suraj, Nethaji Pruthiviraj, Roshan M Borkar and Sudhagar Selvaraju","doi":"10.1039/D5MO00039D","DOIUrl":"10.1039/D5MO00039D","url":null,"abstract":"<p >The development of acquired resistance to tamoxifen poses a significant clinical challenge in breast cancer treatment. Tumour heterogeneity has emerged as a primary reason for the clinical implications of resistance, yet we still lack actionable targets to address this issue. Repurposing existing drugs has become an emerging trend to tackle demanding medical indications. Therefore, we aim to study the efficacy of the antipsychotic drug Thioridazine against both parental and tamoxifen-resistant breast cancer cells. In this study, we have demonstrated that Thioridazine induces phospholipid accumulation, followed by necroptosis in both parental and tamoxifen-resistant breast cancer cell lines. We have shown thioridazine-mediated cytostatic effects through analyses of cell viability, cell count, caspase activation, cell cycle, and p21 expression levels. Moreover, employing a pharmacometabolomics approach, we identified that Thioridazine induces phospholipid accumulation in breast cancer cells. We established that Thioridazine promotes the accumulation of phospholipids rather than neutral lipids in cells <em>via</em> lipid-specific fluorescent quantification and imaging analysis. The phospholipid accumulation triggers necroptosis, which was evaluated through a propidium iodide uptake assay. Thioridazine activates RIP signalling, facilitating the subsequent translocation of pore-forming MLKL to the plasma membrane to initiate necroptosis. The formation of MLKL-induced membrane pores was confirmed using scanning electron microscopy for cell surface visualisation. Furthermore, thioridazine co-treatment enhances the efficacy of tamoxifen in resistant breast cancer cells, augmenting its potential for combinatorial treatment. Altogether, Thioridazine induces phospholipid accumulation followed by necroptosis in both parental and tamoxifen-resistant breast cancer cell lines, highlighting its potential application in breast cancer treatment.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 5","pages":" 496-511"},"PeriodicalIF":2.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Temperature- and time-dependent degradation of mouse tissue proteins: insights into RNA-binding protein stability via mass spectrometry† 小鼠组织蛋白的温度和时间依赖性降解:通过质谱分析了解rna结合蛋白的稳定性。
IF 2.4 4区 生物学
Molecular omics Pub Date : 2025-07-14 DOI: 10.1039/D5MO00020C
Aiswarya Suresh, Nikhil Pallaprolu, Aishwarya Dande, Harish Kumar Pogula, Vipan Kumar Parihar and Ramalingam Peraman
{"title":"Temperature- and time-dependent degradation of mouse tissue proteins: insights into RNA-binding protein stability via mass spectrometry†","authors":"Aiswarya Suresh, Nikhil Pallaprolu, Aishwarya Dande, Harish Kumar Pogula, Vipan Kumar Parihar and Ramalingam Peraman","doi":"10.1039/D5MO00020C","DOIUrl":"10.1039/D5MO00020C","url":null,"abstract":"<p >In proteomics research, samples are frequently stored at −20 °C and −80 °C for extended periods, and assessing protein stability under these conditions is essential. We evaluated protein stability in healthy and diseased mice liver tissues stored at 4 °C, −20 °C, and −80 °C for 0, 7, 30, 90, and 180 days. A 10% variation in protein concentrations (by day 90, <em>p</em> &lt; 0.001) was observed <em>via</em> BCA assay across all conditions. Untargeted proteomic analysis was performed using in-solution trypsin digestion and LC-Q-Orbitrap-MS/MS, with data processed using Proteome Discoverer 2.5. Proteins were shortlisted based on ≥2 unique peptides, FDR &lt; 1%, and abundance ratio <em>p</em> ≤ 0.001. Differentially expressed proteins were identified using log 2 FC ± 2, <em>p</em>-adj ≤ 0.05. Protein degradation varied with storage conditions. In healthy tissues, 24, 11, and 8 proteins completely degraded at 4 °C, −20 °C, and −80 °C, respectively, after 7 days, compared to 8, 2, and 3 proteins in diseased tissues. The total number of significant proteins consistently identified across all time points in healthy samples was 2570, 2711, and 2617, and in diseased samples it was 2124, 2414, and 2353 at 4 °C, −20 °C, and −80 °C, respectively. RNA-binding proteins, such as La ribonucleoprotein 1B, Reticulophagy regulator 3, and Telomerase RNA component interacting RNase, were particularly prone to degradation across all conditions within 7 days. Notably, 18 degraded proteins were reported as biomarkers in disease conditions. Although −20 °C and −80 °C provided better preservation, residual instability persisted. Optimizing storage conditions is essential to prevent degradation, particularly for biomarker discovery studies.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 5","pages":" 479-495"},"PeriodicalIF":2.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信
小红书