Biological Research最新文献

{"title":"Boldo leaves reduce seizures, neuroinflammation, and hemichannel activity in a murine model of chronic epilepsy.","authors":"Claudia García-Rodríguez, Carolina Flores-Muñoz, Paola Fernández, Marcela Escobar, Álvaro O Ardiles, Ana M Cardenas, Juan C Sáez","doi":"10.1186/s40659-025-00647-w","DOIUrl":"10.1186/s40659-025-00647-w","url":null,"abstract":"<p><p>Epilepsy is a chronic neurological disorder characterized by a propensity for seizures due to an imbalance between excitatory and inhibitory brain activity. This condition also induces neuroinflammation, which contributes to disease progression. Given that hemichannels (HCs) permeabilize the cell membrane of glia playing a critical role in neuroinflammation, we investigated the antiepileptic potential of Boldo (Peumus boldus M.), an endemic Chilean tree containing several bioactive molecules including boldine, a HC inhibitor. Mice were treated with pulverized Boldo leaves, the antiseizure medication valproate, or a combination of both for 5 days. Seizure severity was assessed in a pentylenetetrazole-induced kindling mouse model. Using the dye uptake technique, we evaluated the membrane permeability in hippocampal astrocytes, microglia, and neurons. Additionally, we analyzed astroglial and microglial reactivity and measured levels of pro-inflammatory cytokines (IL-1β, IL6, and TNF-α). Both Boldo and valproate significantly reduced seizure severity. However, distinct mechanisms were observed. Valproate administration increased dye uptake in control animals and enhanced glial reactivity, corroborating its established ability to stimulate hemichannel activity. Conversely, Boldo treatment, either alone or in conjunction with valproate, reduced these parameters, consistent with its HC-blocking properties. Importantly, Boldo was more effective than valproate in reducing plasmatic levels of inflammatory and oxidative stress markers. These findings indicate that Boldo, by inhibiting these HCs, could provide a valuable therapeutic strategy to mitigate neuroinflammation in epilepsy, highlighting the clinical potential of this readily available medicinal herb.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"72"},"PeriodicalIF":4.6,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dedifferentiation and metabolic reprogramming of human adipocytes in the tumor niche triggered by colorectal cancer cells.","authors":"Katarzyna Pietraszek-Gremplewicz, Joanna Olszańska, Mikołaj Domagalski, Agata Tymińska, Aneta Skoniecka, Michał Pikuła, Dorota Nowak","doi":"10.1186/s40659-025-00660-z","DOIUrl":"10.1186/s40659-025-00660-z","url":null,"abstract":"<p><p>BACKGROUND: Tumor development and formation are primarily influenced by the interactions of surrounding tissues, and the cells of these become incorporated into the vicinity of the tumor and shape its microenvironment. In particular, adipose tissue plays a pivotal role, and its primary cellular components, adipocytes, make a significant contribution to this process. The multifaceted role of fat cells in the formation and progression of cancer remains an active area of research, and many aspects of this process remain undefined. Thus, the main objective of this study was to investigate how colorectal cancer (CRC) cells influence human-derived adipocytes reprogramming. RESULTS: Our results demonstrate that CRC cells promote the dedifferentiation of adipocytes into a more fibroblast-like phenotype, and this process resulted in the formation of cells with characteristics resembling those of cancer-associated adipocytes (CAAs). Furthermore, co-culture with cancer cells disrupted cytoskeletal homeostasis in adipocytes, which enhanced the formation of actin filaments and led to the development of a more complex vimentin network. This was accompanied by alterations in lipid droplet profiles and the levels of proteins involved in lipid storage and metabolism. Interestingly, CRC cells also modulated the metabolic activity of CAAs and affected their mitochondrial distribution and dynamics. CONCLUSIONS: The results underscore the substantial influence of CRC cells on adipocytes, which may have an essential role in their recruitment into the tumor niche and protumorigenic activity. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"75"},"PeriodicalIF":5.4,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12746635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0003611 hinders the transformation of mesenchymal stem cells into osteosarcoma cells through suppressing MYC by IGF2BP3 via m⁶A modification.","authors":"Fei Zhang, Fei Cheng, Zhiyong He, Chengyi Zhao","doi":"10.1186/s40659-025-00659-6","DOIUrl":"10.1186/s40659-025-00659-6","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is the most common non-hematogenous primary malignancy in the bone. Due to several origins of OS, 30-40% OS patients would experience recurrence and metastasis, with a 5-year survival rate of 20-30%. Mesenchymal stem cells (MSCs) transform into OS cells during the differentiation into osteoblasts, and circular RNA (circRNA) hsa_circ_0003611 might contribute to the differentiation of MSCs into osteoblasts. However, the role of hsa_circ_0003611 in the transformation of MSCs into OS cells is largely unknown. This study aims to investigate whether hsa_circ_0003611 tunes the transformation of MSCs into OS cells.</p><p><strong>Methods: </strong>Here, human bone marrow mesenchymal stem cells (hBMSCs) with hsa_circ_0003611 stably silenced was constructed. Moreover, protein-RNA interaction was detected by RNA immunoprecipitation (RIP), and N⁶-methyladenosine (m⁶A) modification of hsa_circ_0003611 was determined using methylated RNA immunoprecipitation (MeRIP).</p><p><strong>Results: </strong>The present study reveals that hsa_circ_0003611 level is almost absent in OS cells compared to that in osteoblasts and MSCs. Moreover, hsa_circ_0003611 silence enhances the transformation of MSCs into OS cells in vitro and triggered tumorigenicity of MSCs for OS in vivo. Mechanistically, silence of hsa_circ_0003611 promotes the transformation of MSCs into OS cells by activating MYC proto-oncogene, bHLH transcription factor (MYC) via insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3). Moreover, hsa_circ_0003611 silence improves MYC mRNA stability by facilitating the association between IGF2BP3 and MYC mRNA in MSCs. Furthermore, m⁶A modification disrupts the association between hsa_circ_0003611 and IGF2BP3 to enhance the association between IGF2BP3 and MYC mRNA in MSCs.</p><p><strong>Conclusion: </strong>In summary, these findings highlight the role of hsa_circ_0003611 in the transformation of MSCs into OS cells and provide novel targets and strategies for OS treatment.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"2"},"PeriodicalIF":4.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A recent and rapid genome expansion driven by the amplification of transposable elements in the Neotropical annual killifish Garcialebias charrua.","authors":"Felipe Gajardo-Escobar, Camilo Valdivieso, Alex Di Genova, Luisa Pereiro, Maria Jose Arezo, Gino Nardocci, Natalia Rojas, Verónica Gutiérrez, Nicolás G Papa, Nibia Berois, Alex Orellana, Rodrigo A Gutiérrez, Mauricio González, Marco A Mendez, Martín Montecino, Christian Hodar, Alvaro Glavic, Alejandro Maass, Graciela García, Miguel L Allende","doi":"10.1186/s40659-025-00649-8","DOIUrl":"10.1186/s40659-025-00649-8","url":null,"abstract":"<p><p>BACKGROUND: Neotropical annual killifish survive in seasonal ponds due to their ability to undergo embryonic diapauses in the dry season and grow, reproduce and die in the span of a few months during the rainy season. The Austrolebias genus group is endemic to the South American basins and shows remarkable speciation and genetic plasticity. Within this fish group Garcialebias charrua is sympatric with another annual killifish, Cynopoecilus melanotaenia, belonging to a tribe that diverged about 25 million years ago. Despite being closely related species within the Rivulidae family, both species show important differences in genome size. Here, we explore the genomic structure of these species to understand their evolution and unique adaptations. RESULTS: We have sequenced the genomes of G. charrua and C. melanotaenia and determined that they show important structural differences between them. While C. melaotaenia has a genome size of around 1 Gb, similar to that of most characterized teleosts, G. charrua has undergone an evolutionarily recent and massive genome expansion, with a size three times larger (3 Gb). The expansion of the genome in G. charrua has occurred due to amplification of repetitive elements, most recently from the LINE class of elements. We explore and characterize in detail the contribution to genome expansion of repetitive elements at the level of superfamilies, as well as analyze the relationship between these elements and coding genes in G. charrua. We also examine the selection pressures on gene sequences and identify functions that are under positive or purifying selection, and compare these data with that derived from other species. CONCLUSIONS: Our study adds a crucial element to the understanding of annual fish evolution and life history. We show that the genetic variability and plasticity in G. charrua is accompanied by a recent genome-wide expansion with an important contribution of repetitive elements. By comparing these findings with data from other species, we show that G. charrua has undergone bursts of repetitive element expansion, with specific superfamilies of retrotransposons and DNA transposons being the most prevalent and recent. In addition, we characterize genes that are potentially implicated in adaptive traits because of their interaction with mobile elements or because they display evidence of intensified selection. These genes are candidates for functional studies aimed at unraveling the genetic basis of annualism. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"1"},"PeriodicalIF":5.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12763893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyploid giant cancer cells (PGCC): short-term return to multicellularity.","authors":"Alexander E Vinogradov, Olga V Anatskaya","doi":"10.1186/s40659-025-00650-1","DOIUrl":"10.1186/s40659-025-00650-1","url":null,"abstract":"<p><strong>Background: </strong>Polyploidization is associated with progression of cancer, making cancer cells more dangerous. The common polyploid cancer cells constitute a considerable part of tumors (up to 56% in metastases). The giant polyploid cancer cells (PGCC), which appear under severe stress caused by treatment when the majority of cells die, present an enigmatic phenomenon both in fundamental and practical sense because they develop treatment resistance.</p><p><strong>Results: </strong>Using transcriptome meta-analysis, we studied different types of polyploid cancer cells and found that in common polyploid cancer cells, the genes of unicellular (UC) origin and stemness are upregulated (compared to diploid cancer cells). At that, the upregulated UC genes show a higher local and global protein interactome centrality than the upregulated stemness genes, suggesting that the UC interactome attractor is a driving force behind this backward movement along the evodevo axis. Surprisingly, PGCC show the opposite picture. There occurs the suppression of UC and stemness genes with the upregulation of multicellular genes (especially those involved in intercellular communication), suggesting a reversal towards multicellular (MC) state. This effect is enhanced in PGCC's early progeny but diminished in the late progeny, indicating its transient nature. PGCC of different origin (breast, ovarian, prostate cancers), induced by different stresses (radiation or drugs with various mechanisms of action), show a similar behavior. The first principal component of transcriptome profiles, which is common for all cell types (initial cancer cells, PGCC, early and late progeny) and contains the major part of expression variance, is also directed along the gene evolutionary age axis.</p><p><strong>Conclusions: </strong>While the common polyploid cancer cells comply with the 'serial atavism' model of oncogenesis, PGCC present a unique phenomenon of the short-term return to multicellularity probably associated with collective acquisition of resistance to treatment. Our analysis revealed also the evolutionary origin of the main differences in gene expression, emphasizing the importance of gene age axis in transcriptome analyses. The deep evolutionary basis of variation in gene expression across and within cell types might become a general framework for interrelated problems of cell and cancer biology and regenerative medicine.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"58 1","pages":"71"},"PeriodicalIF":4.6,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12642267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A gal4 insertion in the rx3 locus as a tool for visualization and manipulation of eye fated cells in zebrafish.","authors":"María J Vásquez-Ramírez, Aarón Villanueva, Esteban Lira, Daniel Nahuelpan, Koichi Kawakami, Leonardo E Valdivia","doi":"10.1186/s40659-025-00656-9","DOIUrl":"10.1186/s40659-025-00656-9","url":null,"abstract":"<p><p>BACKGROUND: The rx3 gene encodes a transcription factor essential for eye development in zebrafish. Despite its importance, the spatiotemporal dynamics of gene expression during embryogenesis are not fully understood. This knowledge gap, coupled with the limitations of existing genetic tools, highlights the need for novel and more faithful reporters. In this study, we characterized a new transgenic zebrafish line with an insertion of gal4 transcriptional activator in the second exon of the rx3 gene, named tg(gSAIzGFFD2459B), to visualize and analyse gene function. RESULTS: In heterozygous embryos, the gal4 insertion drives gene expression to label eye-fated progenitor cells, providing a valuable tool for dissecting the mechanisms underlying eye formation. Conversely, homozygous gal4 insertion results in a fully penetrant eyeless phenotype, allowing for the continued tracking of rx3-expressing cells within the developing brain. This transgenic line permits intersectional labelling with other UAS-driven transgenes, enabling further exploration of gene function. Remarkably, unlike previously published rx3 reporters that use medaka gene regulatory sequences, our line lacks ectopic expression and provides a more faithful recapitulation of endogenous rx3 expression. CONCLUSION: The tg(gSAIzGFFD2459B) line represents a versatile platform for both studying the developmental gene regulation of eye-fated cells and enhancing our understanding of genetic determinants in vertebrate organogenesis. By reporting rx3 transcriptional activity in both wild-type and mutant states, this transgenic tool supports the critical role of rx3 in eye morphogenesis and offers new avenues for investigating congenital disorders of the eye and brain. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"74"},"PeriodicalIF":5.4,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-130a-3p promotes fiber type transition and improves exercise tolerance in mice.","authors":"Lipeng Xing, Hao Zhou, Haibin Deng, Binghua Yao, Junyi Luo, Ting Chen, Jiajie Sun, Songbo Wang, Gang Shu, Qingyan Jiang, Yongliang Zhang, Qianyun Xi","doi":"10.1186/s40659-025-00644-z","DOIUrl":"10.1186/s40659-025-00644-z","url":null,"abstract":"<p><p>BACKGROUND: Skeletal muscle plays various roles in physiological stress, such as movement, hormone secretion and oxidative metabolism. MicroRNA (miRNA) is involved in skeletal muscle development and fiber type transformation. Our previous studies have shown that miR-130a-3p is an important regulator of glycolipid metabolism and participates in the aerobic oxidation process. However, its potential impact on skeletal muscle development and muscle fiber type transformation by enhancement of aerobic metabolism of nutrients remains unexplored. METHODS: Mice with knockout and overexpression of miR-130a-3p were utilized to investigate its impact on mouse muscle development via assessments of body composition, metabolic activity in cages, and running performance. The influence of miR-130a-3p on muscle cell proliferation, differentiation, and fiber type was assessed following transfection of C2C12 cells. RESULTS: In this study, we found that miR-130a-3p overexpression significantly inhibited weight gain and fat content in mice, while promoting oxidative metabolism and improving exercise tolerance. Upregulation of miR-130a-3p in gastrocnemius (GAS) increased the expression of genes controlling cell proliferation, such as proliferating cell nuclear antigen (PCNA), cyclin D, and cyclin E, and decreased the protein expression of myosin heavy chain (MyHC), myogenic differentiation 1 (MyoD) and myopoietin (MyoG). In addition, miR-130a-3p overexpression significantly increased the proportion of type I fibers and decreased the proportion of type IIB fibers in GAS. These phenotype were also observed when miR-130a-3p was overexpressed in differentiated C2C12 myoblasts. Mechanistically, miR-130a-3p can promote the proliferation of myoblasts and inhibit the differentiation of myoblasts. Importantly, miR-130a-3p was proved to target the transforming growth factor beta receptor 2 (TGFβR2). Taken together, miR-130a-3p could be a potential therapeutic target that regulates fiber type conversion during skeletal muscle development and improves skeletal muscle energy metabolism during exercise through regulating TGFβR2 signalling pathway. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"58 1","pages":"70"},"PeriodicalIF":5.4,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12628931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene expression changes in pancreatic α-cell lines following knock-out Of either CK2α or CK2α'.","authors":"Jens Mayer, Mandy Pack, Mathias Montenarh, Claudia Götz","doi":"10.1186/s40659-025-00654-x","DOIUrl":"10.1186/s40659-025-00654-x","url":null,"abstract":"<p><strong>Background: </strong>Protein kinase CK2 is known to exist as a tetramer of two catalytic α- or α'- subunits and two non-catalytic β-subunits, or as multimers of this tetramer. Moreover, CK2α (CSNK2A1) and CK2α' (CSNK2A2) are also active in the absence of CK2β (CSNK2B). Very little is known about specific functions of the individual subunits of protein kinase CK2.</p><p><strong>Results: </strong>In order to study the effects of CK2α and CK2α' on gene expression, we used the Mus musculus pancreatic α-cell line αTC1 and two derivatives with either CK2α (KO1 cells) or CK2α' (KO2 cells) expression knocked-out by CRISPR/Cas technology. We found numerous genes deregulated in both KO1 and KO2 cells compared to the parental cells. Applying stringent thresholds, 266 genes were found down-regulated and 153 genes up-regulated in KO1 cells, 233 genes were found down-regulated and 84 genes up-regulated in KO2 cells. Dozens of genes were found deregulated in a similar fashion in both KO1 and KO2 cells. We found altered expression of genes involved in the differentiation of pancreatic cells, including Hox genes, and in the regulation of glucagon synthesis or secretion. Moreover, many of the deregulated genes play an important role in developmental processes and in neuronal cell biology.</p><p><strong>Conclusion: </strong>Our findings reveal individual and shared functions of the CK2α and CK2α' catalytic subunits, in particular regarding their involvement in regulating gene expression.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"58 1","pages":"69"},"PeriodicalIF":4.6,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12616906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methionine deficiency causes spermatogonial apoptosis via oxidative stress and DNA damage response pathway.","authors":"Weiyong Wang, Yong Ruan, Gong Ting","doi":"10.1186/s40659-025-00652-z","DOIUrl":"10.1186/s40659-025-00652-z","url":null,"abstract":"<p><p>Methionine serves as an essential amino acid regulating de novo protein synthesis and redox homeostasis. Previous studies have established adverse impacts of methionine restriction and deprivation on semen quality, but effects on early spermatogenesis remain poorly characterized. In this study, a methionine dietary model (0.86%, 0.17%, 0%) was used to investigate the role of methionine in early spermatogenesis. The results indicated that methionine deprivation caused spermatogenesis defects by inhibiting spermatogonial proliferation and increasing apoptosis. Further studies showed that methionine deprivation downregulated mitochondrial function-related genes (Gpx4, Fis1 and Gstm1), but upregulated ISR- (Atf4, Chac1 and Ddit3) and DNA damage response-related genes (Cdkn1a, Chek2 and Atm). Meanwhile, methionine deprivation caused mitochondrial dysfunction characterized by mitochondrial membrane potential depolarization, ROS accumulation, and MitoSOX accumulation. Methionine deprivation also caused an obvious increase in DNA damage response proteins (γH2AX, p-CHK2 and p-p53) and pro-apoptotic proteins (PUMA, BAX and c-PARP1), but suppressed anti-apoptotic protein BCL2. Furthermore, NAC effectively reversed the proliferation deficiency of GC-1 cells caused by methionine deprivation. Collectively, these findings suggest that methionine deprivation triggers ISR activation, which subsequently induces spermatogonial apoptosis via oxidative stress and the CHK2-p53/p21 signaling cascade. This study highlights the critical role of methionine in early spermatogenesis, provides mechanistic insights for optimizing dietary interventions and addresses related reproductive disorders.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"58 1","pages":"68"},"PeriodicalIF":4.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12606962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The nuclear receptor NR6A1 plays an oncogenic role through reprogramming glycolysis in tumors.","authors":"Xiaowen Liu, Ye Li, Xinxu Rao, Shun Xie, Zhuoxian Rong, Lifang Yang, Zenghui Enghui Mao, Dan Li","doi":"10.1186/s40659-025-00646-x","DOIUrl":"10.1186/s40659-025-00646-x","url":null,"abstract":"<p><p>NR6A1 is a member of the nuclear receptor superfamily of ligand-activated transcription factors and can bind to conserved DNA sequences, acting as a transcriptional repressor. NR6A1 has been reported to promote prostate cancer, gastric cancer, and testicular germ cell tumor progression. In the present study, we confirmed the oncogenic role of NR6A1 in several types of cancer cells, including HeLa, TFK1, and A549 cells, and revealed that NR6A1 knockdown led to a decrease in lung adenocarcinoma cell proliferation, a reduction in glucose consumption, a reduction in lactic acid production, and decreases in ATP levels and mitochondrial membrane potential. Mechanistically, through a series of methods, including bioinformatics analysis, dual-luciferase reporter gene assay, RT-qPCR, Western blot analysis, and functional rescue experiments, we demonstrated that NR6A1 may promote the expression of HK1 by directly suppressing miR-302a, thereby reprogramming tumor cell glycolysis and enhancing lung adenocarcinoma cell growth. In addition, we found that NR6A1 can affect mTOR signaling, suggesting a broader role in tumor metabolism regulation. In summary, our data indicate that NR6A1 plays an oncogenic role by reprogramming glycolysis via the miR-302a/HK1 axis in lung adenocarcinoma.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"58 1","pages":"67"},"PeriodicalIF":4.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12606860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}