{"title":"Integrative transcriptomics and metabolomics reveal distinct metabolic reprogramming in luminal and triple-negative breast cancer cells.","authors":"Preeti Ranawade, Babasaheb Sonwane, Ganesh Bose, Revati Jadhav, Rakesh Joshi, Smriti Mittal","doi":"10.1093/momics/aaiaf003","DOIUrl":"https://doi.org/10.1093/momics/aaiaf003","url":null,"abstract":"<p><p>Breast cancer subtypes exhibit significant molecular and metabolic heterogeneity, influencing their aggressiveness and therapeutic responses. Among them, triple-negative breast cancer (TNBC) is highly aggressive and often resistant to conventional therapies. To investigate the metabolic programming of this aggressiveness, we conducted an integrated transcriptomics and metabolomics analysis comparing the MCF-7 (luminal A, ER+/PR+) and MDA-MB-231 (TNBC) breast cancer cell lines. Transcriptome analysis of MCF-7 and MDA-MB-231 revealed the differential expression of genes involved in key metabolic pathways. Metabolomics data, further corroborated by transcriptomics, suggest pathway enrichment in beta-alanine, histidine, glutathione, nucleotide metabolism, and the tricarboxylic acid cycle. MDA-MB-231 cells displayed a metabolically aggressive phenotype with enhanced oxidative phosphorylation, redox adaptation, and nucleotide turnover. In contrast, MCF-7 cells showed a more regulated amino acid and redox metabolism profile. The integration of transcriptomic and metabolite profiles highlighted potential metabolic vulnerabilities in TNBC, offering insights into subtype-specific differences at the molecular level.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":"22 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202249","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}
{"title":"Urine metabolomics for seronegative rheumatoid arthritis: an exploratory dual-platform analysis.","authors":"Koteswari Peddi, Satyanarayana Swamy Cheekatla, Usharajeswari Davulury, Prathyash Ushus M J, Satish Mutyam, Siva Kumar Kandula, Vishnu Vardhan Reddy Munagala, Sivakumar Vallabhapurapu","doi":"10.1093/momics/aaiaf004","DOIUrl":"https://doi.org/10.1093/momics/aaiaf004","url":null,"abstract":"<p><p>Seronegative rheumatoid arthritis (negRA) is difficult to diagnose due to the absence of rheumatoid factor and anticitrullinated peptide antibodies. This observational case-control study analysed urine samples from 35 negRA patients and 25 healthy controls using integrated liquid chromatography-quadrupole time-of-flight mass spectrometry and gas chromatography-mass spectrometry. Data were processed using mass spectrometry-data independent analysis and evaluated with multivariate approaches, including orthogonal partial least squares discriminant analysis and receiver operating characteristic curve analysis. We identified distinct urinary metabolic alterations in negRA, with four metabolites showing moderate-to-excellent diagnostic accuracy (area under the curve: 0.78-0.91). Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes indicated the involvement of redox regulation and nucleotide/cofactor metabolism. These findings support the potential of urine metabolomics as a non-invasive tool for biomarker discovery in negRA and warrant validation in larger cohorts.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":"22 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201756","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}
Molecular omicsPub Date : 2026-01-10DOI: 10.1093/momics/aaiaf005
Zhiyan Li, Luyao Yu, Xingyu Liu, Liangle Deng, Zongtao Lin, Zhuocheng Liu, Benjamin A Garcia, Yixuan Xie
{"title":"Development of an immobilized system for RNA modification analysis.","authors":"Zhiyan Li, Luyao Yu, Xingyu Liu, Liangle Deng, Zongtao Lin, Zhuocheng Liu, Benjamin A Garcia, Yixuan Xie","doi":"10.1093/momics/aaiaf005","DOIUrl":"10.1093/momics/aaiaf005","url":null,"abstract":"<p><p>Characterizing RNA modifications is crucial for understanding fundamental biological processes, such as RNA folding, stability, translation, and splicing. However, current systems for ribonucleoside sample preparation are limited to the solution phase. In this study, we employed the click reaction between methyltetrazine and trans-cyclooctene to immobilize RNases, including nuclease P1, phosphodiesterase I, and shrimp alkaline phosphatase, on agarose beads. Using this digestion method, RNA was fully converted to ribonucleosides within 30 min. Importantly, integrating these immobilized RNases with a microspin tube modified with porous graphitic carbon enabled direct downstream MS analysis, constituting a streamlined system. We applied this system to monitor RNA modification dynamics during transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition in lung cancer cells and observed significant changes in several RNA modifications (e.g. m6A and m5U), which is consistent with the indispensable role of RNA modifications in tumour metastasis. Overall, our results demonstrate the efficiency and robustness of our method and highlight a promising direction for RNA modification analysis, supporting the development of automated, high-throughput workflows for future large-cohort studies.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":"22 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12851623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Subhajit Karmakar, Mouli Chatterjee, Malini Basu and Mrinal K Ghosh
{"title":"STUB1 (CHIP) – a prognostic marker in cancer","authors":"Subhajit Karmakar, Mouli Chatterjee, Malini Basu and Mrinal K Ghosh","doi":"10.1039/D5MO00205B","DOIUrl":"10.1039/D5MO00205B","url":null,"abstract":"<p > <em>STUB1</em>, also known as CHIP (C-terminus of Hsc70-Interacting Protein), plays a vital role in cellular protein homeostasis through its E3 ubiquitin ligase activity. Recent evidence suggests that <em>STUB1</em> (CHIP) is implicated in various cancer types, influencing tumorigenesis by regulating the degradation of oncogenic and tumor suppressor proteins, <em>viz.</em>, c-Myc, PTEN, p53 <em>etc.</em> This study investigates the prognostic value of <em>STUB1</em> across multiple cancers through a comprehensive pan-cancer analysis utilizing large public databases, including The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) and further validation of results in multiple cancer cell lines. Our analysis reveals distinct expression patterns of <em>STUB1</em> (CHIP) across different cancer types and highlights its correlation with clinical outcomes. In certain cancers, high <em>STUB1</em> (CHIP) expression is associated with worse prognosis, likely due to its role in degrading tumor suppressor proteins. Conversely, in other cancer types, low <em>STUB1</em> (CHIP) expression correlates with poor survival, possibly due to impaired degradation of oncogenic factors. The study provides crucial insights into the dual roles of <em>STUB1</em> (CHIP) in several cancer types, establishing it as a potential prognostic marker. Our investigation into the contextual role of <em>STUB1</em> (CHIP) within human tissue samples, employing immunoblotting and complementary assays, highlights its potential as a therapeutic target for restoring protein homeostasis and modulating cancer progression. Nonetheless, further research is necessary to comprehensively elucidate the mechanisms by which <em>STUB1</em> (CHIP) regulates tumorigenesis across various cancer types.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 768-793"},"PeriodicalIF":2.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549942","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}
{"title":"DeSciDe: a tool for unbiased literature searching and gene list curation unveils a new role for the acidic patch mutation H2A E92K","authors":"Cameron J. Douglas and Ciaran P. Seath","doi":"10.1039/D5MO00160A","DOIUrl":"10.1039/D5MO00160A","url":null,"abstract":"<p >Omics analysis has become an indispensable tool for researchers in the life sciences, enabling the study of DNA, RNA, and proteins and how they respond to cellular stimulus. Many methods of data analysis exist for the generation and characterization of gene lists, however, selection of genes for further investigation is still heavily influenced by prior knowledge, with practitioners often studying well characterized genes, reinforcing bias in the literature. Here, we have developed an open-source, R package for impartial ranking of gene lists derived from omics analysis that we term deciphering scientific discoveries (DeSciDe). We applied a pipeline that sorts a gene list first by precedence, which we define as co-occurrence of the gene with pre-defined search terms in publications. We then rank gene lists by connectivity, an underutilized metric for how related a gene is to other enriched genes. The combination of these rankings by scatterplot provides a method for gene selection by simple visual analysis. We apply this analysis method to published Omics datasets, identifying novel avenues for investigation. Further, using this method we have been able to assign a novel loss of function role for the histone mutation H2A E92K.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 760-767"},"PeriodicalIF":2.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12599656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Motseoa Mariam Lephatsi, Mpho Susan Choene, Abidemi Paul Kappo, Ntakadzeni Edwin Madala and Fidele Tugizimana
{"title":"Mapping the Helichrysum metabolome: uncovering species-specific chemistry through an AI-guided LC-MS/MS workflow","authors":"Motseoa Mariam Lephatsi, Mpho Susan Choene, Abidemi Paul Kappo, Ntakadzeni Edwin Madala and Fidele Tugizimana","doi":"10.1039/D5MO00118H","DOIUrl":"10.1039/D5MO00118H","url":null,"abstract":"<p > <em>Helichrysum</em> species, of which 35% are native to South Africa, are renowned for their diverse medicinal properties, yet their chemical composition remains largely unexplored. As such, continuous efforts are needed to comprehensively characterize the phytochemistry of <em>Helichrysum</em> species which will subsequently contribute to the discovery and exploration of <em>Helichrysum</em>-derived natural products for drug discovery. Thus, a computational metabolomics work is reported herein to comprehensively characterize the metabolic landscape of three medicinal species (<em>H. italicum</em>, <em>H. petiolare</em>, and <em>H. splendidum</em>), which are less studied. The metabolites were extracted using hexane, ethyl acetate, and methanol and analyzed on a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. Different solvents were utilized to increase metabolome coverage in <em>Helichrysum</em> species. Spectral data were mined using molecular networking (MN) strategies. The results revealed that multiple extraction methods provide a more comprehensive analysis of the metabolome of the three plants. The measured metabolome of <em>Helichrysum</em> species is rich in phenylpropanoids, lipids and lipid-like molecules, pointing to a rich chemistry with potential bioactivities. Comparative analysis of the <em>H. italicum</em>, <em>H. petiolare</em> and <em>H. splendidum</em> metabolomes revealed that the flavonoid glucoside and triterpenoid profiles of the three species differ distinctively. These results expand the knowledge base on the chemistry of <em>Helichrysum</em> plants and provide deconvoluted details of the various chemical classes that differentially define the metabolome of the <em>Helichrysum</em> plants. Such actionable insights point to <em>Helichrysum</em>'s potential as a valuable source of natural compounds with promising medicinal properties.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 747-759"},"PeriodicalIF":2.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/mo/d5mo00118h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prema Kumari Agarwala, Avinash Singh, Sanjeeva Srivastava and Shobhna Kapoor
{"title":"Hypoxia-induced alterations in lipid polyunsaturation and associated proteins drive aggressive metastasis in pancreatic cancer via the PPAR/hypoxia pathway","authors":"Prema Kumari Agarwala, Avinash Singh, Sanjeeva Srivastava and Shobhna Kapoor","doi":"10.1039/D5MO00111K","DOIUrl":"10.1039/D5MO00111K","url":null,"abstract":"<p >In pancreatic ductal adenocarcinoma, hypoxia is a crucial component of the tumour microenvironment and is associated with worse clinical outcomes. Adaptation to extreme hypoxic settings is based on abnormal lipid metabolism, but insights into how hypoxia-regulated lipid changes link with aggressive migratory potential in pancreatic cancer are lacking. This study investigates the molecular processes, pathways, and critical proteins involved in hypoxia-induced lipidic and polyunsaturated fatty acid alterations in pancreatic cancer. Our findings elucidate increased multilayer unsaturation in FA chains of major lipid classes associated with greater migration and invasion, as well as higher abundances of particular desaturases. The expression of these proteins was verified in clinical tumour samples by unsaturated fatty acid biosynthesis-related gene enrichment score. High unsaturated fatty acid clusters were shown to be associated with a low survival rate. Pathway correlation and protein–protein interaction analysis indicated that the PPAR-hypoxia axis and SCD/FADS2/APOC3-HDLBP protein network are implicated in mediating the observed alterations in lipid pools and poly-unsaturation levels in pancreatic cancer under hypoxia. These results provide novel therapeutic targets in pancreatic cancer while improving our understanding of hypoxia-induced migratory potential in pancreatic cancer.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 736-746"},"PeriodicalIF":2.4,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438422","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}
Eitan Erez Zahavi, Ida Rishal, Juan A. Oses-Prieto, Alexander Brandis, Sergey Malitsky, Maxim Itkin, Šárka Pokorná, Florencia Cabrera-Cabrera, Natjan-Naatan Seeba, Robert Risti, Aivar Lõokene, Anthony H. Futerman, Alma L. Burlingame, Mike Fainzilber and Indrek Koppel
{"title":"Nucleolin perturbation alters membrane lipid homeostasis","authors":"Eitan Erez Zahavi, Ida Rishal, Juan A. Oses-Prieto, Alexander Brandis, Sergey Malitsky, Maxim Itkin, Šárka Pokorná, Florencia Cabrera-Cabrera, Natjan-Naatan Seeba, Robert Risti, Aivar Lõokene, Anthony H. Futerman, Alma L. Burlingame, Mike Fainzilber and Indrek Koppel","doi":"10.1039/D5MO00088B","DOIUrl":"10.1039/D5MO00088B","url":null,"abstract":"<p >AS1411 is a G-rich DNA aptamer that targets the multifunctional RNA-binding protein nucleolin. AS1411 has both antiproliferative and cell size-regulating activities and has been evaluated for clinical utility, reaching phase II trials as an anticancer agent. The mechanisms underlying cell size effects of AS1411 are not well understood and broad characterization of its molecular effects is lacking. Here, we used a multi-omics approach to profile transcriptome, proteome and lipidome changes in AS1411-treated NIH-3T3 cells, which increase in size in response to the aptamer. We found that AS1411 caused downregulation of cholesterol biosynthesis pathway enzymes at both mRNA and protein levels, without an accompanying reduction in cellular cholesterol levels or cholesterol uptake. In addition, AS1411 induced changes in several lipid classes, including increases in phosphatidylethanolamine levels. Ratiometric imaging of Di-4-ANEPPS-labeled cells showed that AS1411 decreases the fluidity of intracellular membranes. Thus, aptamer engagement of nucleolin affects lipid biosynthesis and homeostasis, likely contributing to its roles in cell size control.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 723-735"},"PeriodicalIF":2.4,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12560814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145378130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuki Ishino, Yuta Shimanaka, Junken Aoki and Nozomu Kono
{"title":"Mass spectrometry-based profiling of phosphoinositide: advances, challenges, and future directions","authors":"Yuki Ishino, Yuta Shimanaka, Junken Aoki and Nozomu Kono","doi":"10.1039/D5MO00115C","DOIUrl":"10.1039/D5MO00115C","url":null,"abstract":"<p >Phosphoinositides (PIPs), the phosphorylated derivatives of phosphatidylinositol (PI), are low-abundance yet critical components of eukaryotic membranes. They play pivotal roles in a wide array of cellular processes, including signal transduction, membrane trafficking, and cell motility. The seven PIP subclasses, generated by phosphorylation at the 3-, 4-, and 5-positions of the inositol ring, are tightly regulated in both spatial and temporal contexts. Dysregulation of PIP metabolism is associated with a range of diseases, including cancer, myopathy, and neurodegenerative and developmental disorders. While the importance of phosphorylation of the inositol ring is well established, recent studies have clarified the role of the fatty acyl chain composition of PIPs. This has resulted in a growing interest in analytical techniques that can determine fatty acyl chain profiles of PIPs. Over the past three decades, substantial advances have been made in mass spectrometry-based techniques, enabling detailed characterization of PIP molecular species, including their phosphate regioisomers. This review provides an overview of the development of mass spectrometric methods for analyzing PIPs, with a particular focus on those enabling the separation of PIP regioisomers and the profiling of their acyl chain composition.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 536-544"},"PeriodicalIF":2.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/mo/d5mo00115c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145378119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}