Archives of biochemistry and biophysics最新文献

{"title":"Uncoupling protein 1 deficiency leads to transcriptomic differences in livers of pregnancy female mice and aggravates hepatic steatosis","authors":"Gang Wei ,&nbsp;Feng-Jie Shen ,&nbsp;Jun-Li Liu ,&nbsp;Jian-Hua Zhao ,&nbsp;Fang-Yuan Yang ,&nbsp;Ruo-Qi Feng ,&nbsp;Jing Lu ,&nbsp;Chen-Yang Zhang ,&nbsp;Feng-Wei Wang ,&nbsp;Bei-Dong Chen ,&nbsp;Xin Ding ,&nbsp;Jin-Kui Yang","doi":"10.1016/j.abb.2025.110395","DOIUrl":"10.1016/j.abb.2025.110395","url":null,"abstract":"<div><div>Pregnancy requires the coordination of metabolically active organs to support maternal nutrition and fetal growth. However, the metabolic cross-talk between adipose tissue and liver in females during pregnancy is still less clear. In this study, we evaluated the metabolic adaptations and phenotypes of liver in response to pregnancy-associated metabolic stress, particularly in the context of genetic ablation of Uncoupling protein 1 (<em>Ucp1)</em>-mediated catabolic circuit. Our results revealed that <em>Ucp1</em> deficiency (UCP1 knockout, KO) mice during late pregnancy exhibited significantly deteriorated metabolic phenotypes, including hepatic steatosis and whole-body glucose and lipid homeostasis, as compared to <em>Ucp1</em> deficiency or normal pregnancy mice. However, non-pregnant <em>Ucp1</em> deficiency mice displayed nearly normal metabolic phenotypes and structure alterations similar to those of littermate controls. Moreover, transcriptomic analyses by RNA sequencing (RNA-seq) clearly revealed that <em>Ucp1</em> deficiency led to a significant liver metabolic remodeling of differentially express genes (DEGs) before and especially during pregnancy. Consistently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated the potential altered functions and signaling pathways, including metabolic dysfunctions in ribosome, oxidative phosphorylation, etc. Importantly, as derived from trend analyses of DEGs, our results further revealed the distinct expression pattern of each subcluster, which coincided with potential biological functions and relevant signaling pathways. The findings in the present study might provide valuable insights into the molecular mechanism of metabolic dysfunction-associated fatty liver disease (MAFLD) during pregnancy. Additionally, our data may provide a novel animal model of MAFLD, thus facilitating its potential therapies.</div></div><div><h3>New &amp; noteworthy</h3><div>Genetic ablation of <em>Ucp1</em> during pregnancy increases hepatic steatosis and deteriorated whole-body glucose and lipid homeostasis. Moreover, changes in hepatic gene expression are closely associated with metabolic dysfunctions in ribosome and oxidative phosphorylation. This work highlights the therapeutic potential of targeting UCP1- mediated catabolic circuit between adipose and liver during pregnancy, and the utility of RNA-seq analysis to reveal valuable information for the distinct expression pattern of each subcluster that contribute to pregnancy-dependent MASLD progression.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110395"},"PeriodicalIF":3.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naringin in repairing articular cartilage injury by activating TGF-β/Smad signaling pathway to attenuate inflammatory response","authors":"Tiancheng Lyu ,&nbsp;Xiangchun Liu ,&nbsp;Yuxuan Liu ,&nbsp;Zheng Yang ,&nbsp;Pengyang Li ,&nbsp;Yingdong Lu ,&nbsp;Pengyuan Zhao ,&nbsp;Jing Chen ,&nbsp;Chao Ye","doi":"10.1016/j.abb.2025.110396","DOIUrl":"10.1016/j.abb.2025.110396","url":null,"abstract":"<div><div>Naringin protects cartilage and attenuates inflammation. This study investigated the mechanism by which naringin activates the TGF-β/Smad signaling pathway to attenuate the inflammatory response and repair rabbit articular cartilage injury. A ring bone extraction drill was used to create a rabbit articular cartilage injury model. Sixteen Japanese white rabbits were divided into Sham, Mod, Nar, and Con groups and treated for 12 weeks. Compared with the Mod group, obvious signs of morphological and structural repair of cartilage injury were observed in the Nar group. The ICRS, BV/TV, and BS/TV scores increased, whereas the Wakitani and Tb.Sp scores decreased. Furthermore, ADAMTS-5 levels were significantly reduced, and TGF-β1 levels were significantly increased. The average light density of P-Smad3 in the repaired tissue was significantly elevated, whereas that of MMP-13 was significantly reduced. Compared with that in the Sham group, the transcription and expression levels of TβRII, type II collagen, P-TβRII, and P-Smad2 in the repair tissues of the Mod group were lower. This was reversed in the Nar group. Therefore, naringin administration can improve the morphology and structure of articular cartilage injury, reduce the concentration and expression levels of pro-inflammatory factors in the joint fluid and repair tissues, and increase the concentrations and expression levels of anti-inflammatory factors in the joint fluid and repair tissues. Thus, naringin exerts a positive effect by reducing the inflammatory response and repairing articular cartilage injury. This mechanism is closely related to the activation of the TGF-β/Smad signaling pathway.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110396"},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights from selenoprotein I mouse models for understanding biological roles of this enzyme","authors":"Lance G.A. Nunes,&nbsp;Chi Ma,&nbsp;Matthew W. Pitts,&nbsp;Peter R. Hoffmann","doi":"10.1016/j.abb.2025.110394","DOIUrl":"10.1016/j.abb.2025.110394","url":null,"abstract":"<div><div>Selenoprotein I (selenoi) is a metabolic enzyme expressed in a wide variety of tissues that catalyzes the transfer of the ethanolamine phosphate group from CDP-ethanolamine to lipid acceptors to generate ethanolamine phospholipids. It is a member of the selenoprotein family, a class of proteins that mostly play fundamental roles in redox homeostasis and are defined by the co-translational incorporation of selenium in the form of selenocysteine. Loss-of-function mutations in the human SELENOI gene have been found in rare cases leading to a complex form of hereditary spastic paraplegia. Understanding the roles of this selenoprotein and its phospholipid products in different cell types has benefited from the development of mouse models. In particular, global and conditional knockout (KO) of the Selenoi gene in mice has enabled a more complete picture to emerge of how this important selenoprotein is integrated into metabolic pathways. These data have revealed how Selenoi loss-of-function affects embryogenesis, neurodevelopment, the immune system and liver physiology. This review summarizes the insights gained through mouse model experiments and the current understanding the different physiological roles played by this selenoprotein.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110394"},"PeriodicalIF":3.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic effects and mechanisms of alcohol extracts from Polygala fallax Hemsl on endometriosis in rats","authors":"Si Yuwen ,&nbsp;Qian Zheng ,&nbsp;Chunhong Liao ,&nbsp;Lijuan Wei ,&nbsp;Sufang Yang ,&nbsp;Ning Li","doi":"10.1016/j.abb.2025.110393","DOIUrl":"10.1016/j.abb.2025.110393","url":null,"abstract":"<div><div>Endometriosis is a chronic estrogen-dependent inflammatory disease that significantly affects women's health. <em>Polygala fallax Hemsl.</em> (PFH), a traditional Zhuang medicine, has been frequently used for gynecological disorders. This study investigated the therapeutic effects and mechanisms of the alcohol extract of <em>Polygala fallax Hemsl.</em> (ae-PFH) in a rat model of endometriosis, as well as its potential for combination therapy. SD rats were divided into seven groups: control, model, PFH, mifepristone, PFH combined with mifepristone, exosomes, and PFH combined with exosomes. After 21 days of treatment, body weight, organ coefficients, and histopathological changes in uterine and ovarian tissues were analyzed. UPLC-Q-Exactive Orbitrap-MS identified active components in ae-PFH and serum samples, followed by molecular docking with key disease target proteins. Serum levels of inflammatory cytokines and hormones were measured using ELISA, while protein and mRNA expression of key regulatory factors were assessed via Western blot and q-PCR. Ae-PFH reduced lesion size and suppressed inflammation, angiogenesis, and pain by inhibitied the PI3K/AKT pathway. Additionally, in combination therapy, ae-PFH significantly enhanced therapeutic effects of mifepristone or exosomes derived from umbilical cord mesenchymal stem cells. These findings indicated that ae-PFH presentd a promising medical method for the treatment of endometriosis, exhibiting innovative potentiality for combination therapy.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110393"},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing cryo-enzymatic efficiency in cold-adapted lipase from Psychrobacter sp. C18 via site-directed mutagenesis","authors":"Fatemeh Balaei ,&nbsp;Khadijeh Pouraghajan ,&nbsp;Soheila Mohammadi ,&nbsp;Sirous Ghobadi ,&nbsp;Reza Khodarahmi","doi":"10.1016/j.abb.2025.110388","DOIUrl":"10.1016/j.abb.2025.110388","url":null,"abstract":"<div><div>As industrial demands for cold-active enzymes have been increased, psychrophilic lipases present a promising solution with potential for innovation and growth in food, pharmaceutical, and detergent industries. Cold-adapted enzymes achieve high catalytic efficiency at low temperatures through their structural flexibility and conformational adaptability. Therefore, in this study, the lipase gene from <em>Psychrobacter</em> sp. C18 was cloned and subjected to site-directed mutagenesis based on computer aided predictions to enhance the enzyme's cold-adapted properties and flexibility. Mutations were strategically selected in loops of the active site to improve the enzyme's accessibility to the substrate under cold conditions. The P163G, L186G, and Q239W mutations were selected for further analysis. Enzyme activity, along with its stability and structural flexibility, was assessed using techniques including UV–Vis spectroscopy, fluorescence, and circular dichroism (CD) spectroscopy. The obtained data revealed that the optimal temperature for the wild-type lipase was 30 °C, which shifted to lower temperatures in the mutants: 15 °C for P163G and L186G, and 20 °C for Q239W. Additionally, the optimal pH of the mutant lipases shifted to more alkaline conditions compared to the wild-type enzyme. While the thermal and pH stability of the mutant enzymes slightly decreased, these findings can be attributed to their enhanced flexibility. Far-UV CD spectroscopy revealed a reduction in <em>α</em>-helical content of the mutant enzymes. Molecular dynamics simulations corroborated these findings, confirming increased structural flexibility in all three mutants compared to the wild-type enzyme. This research underlines the importance of applying engineered cold-adapted enzymes for industrial application.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110388"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and synthesis of pyridopyrimidines targeting NEK6 kinase","authors":"Paolo Zardi ,&nbsp;Benedetta Righino ,&nbsp;Davide Pirolli ,&nbsp;Matteo Gramanzini ,&nbsp;Alessandro Semeraro ,&nbsp;Juan José Galano-Frutos ,&nbsp;Anna Königs ,&nbsp;Luka Ðorđević ,&nbsp;Michele Maggini ,&nbsp;Marianna Buttarelli ,&nbsp;Natalia Cappoli ,&nbsp;Viviana Romano ,&nbsp;Marta De Donato ,&nbsp;Daniela Gallo ,&nbsp;Giovanni Scambia ,&nbsp;Maria Cristina De Rosa","doi":"10.1016/j.abb.2025.110391","DOIUrl":"10.1016/j.abb.2025.110391","url":null,"abstract":"<div><div>We designed a series of pyrido[2,3-<em>d</em>]pyrimidine derivatives based on the structure of the NEK6 kinase inhibitor, compound <strong>21</strong> (2-amino-5-phenyl-5,11-dihydro-3H-indeno[2′,1':5,6]pyrido[2,3-<em>d</em>]pyrimidine-4,6-dione), which share the same heterocyclic core. Chemical modifications, aimed at altering the molecular planarity of <strong>21</strong> to enhance water solubility, were guided by receptor-based ligand design and further supported by molecular docking, molecular dynamics simulations, and free energy perturbation calculations. Our results indicate that disrupting the planarity of <strong>21</strong> increases aqueous solubility ― nearly doubling it in two cases― while reducing lipophilicity. Among the compounds tested, three showed both improved solubility and NEK6 inhibitory activity exceeding 50 % in single-dose assay.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110391"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pericentriolar material 1 aggregation maintains cell survival upon prolonged replication stress","authors":"Yung-Chieh Tsai ,&nbsp;Tian-Ni Kuo ,&nbsp;Yu-Ying Chao ,&nbsp;Ruei-Ci Lin ,&nbsp;Han-Hsiang Chien ,&nbsp;I-Ting Peng ,&nbsp;Yueh-Fong Tsai ,&nbsp;Ping-Jui Su ,&nbsp;Chia-Yih Wang","doi":"10.1016/j.abb.2025.110383","DOIUrl":"10.1016/j.abb.2025.110383","url":null,"abstract":"<div><div>The centrosome is essential for maintaining cell shape and facilitating cell division. Thus, precise control of centrosome copy numbers is crucial for proper chromosome segregation. Pericentriolar material 1 (PCM1) is a scaffold component of centriolar satellites—electron-dense granules dispersed around the centrosome—that regulate the centrosome or primary cilia. It has been shown that disrupting PCM1 aggregation by treating cells with sodium orthovanadate inhibits centrosome amplification. However, sodium orthovanadate is a protein tyrosine phosphatase and may have off-target effects on the centrosome. To further confirm the role of PCM1 aggregation in promoting centrosome amplification, we disrupted PCM1 aggregation by interfering with microtubule networks, inhibiting the dynactin motor complex, or depleting PCM1. Centrosome copy numbers were then examined under conditions of prolonged replication stress. Our data suggest that PCM1 aggregation does not promote centrosome amplification in osteosarcoma U2-OS or pancreatic ductal adenocarcinoma PANC-1 cell lines. Instead, we found that centrosome amplification promoted PCM1 aggregation in a PLK4-dependent manner. Furthermore, we observed that PCM1 depletion inhibited U2-OS cell survival under prolonged replication stress. Prolonged replication stress induced DNA damage signaling via the ATM-CHK1 axis and autophagy to maintain cell survival, while PCM1 depletion alleviated ATM, CHK1, and autophagy activity, thereby reducing cell survival. Our findings propose that PCM1 does not facilitate centrosome amplification but instead induces activation of the ATM-CHK1 axis and autophagy to sustain osteosarcoma cell viability during prolonged replication stress.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110383"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippuric acid, a uremic toxin, binds to aggregation prone region of human lysozyme and potentiates the fibrillation: A biophysical insight","authors":"Nida Zaidi ,&nbsp;Nawaz Akhter ,&nbsp;Muhammad Uzair Ashraf ,&nbsp;Owais Ahmad ,&nbsp;Md Nadir Hassan ,&nbsp;Maryam Khursheed ,&nbsp;Rizwan Hasan Khan","doi":"10.1016/j.abb.2025.110392","DOIUrl":"10.1016/j.abb.2025.110392","url":null,"abstract":"<div><div>End-stage renal disease (ESRD) and human lysozyme (HL) amyloidosis are often interconnected, typically marked by elevated levels of uremic toxins in patients' blood. In this context, hippuric acid (HA), a uremic toxin derived from the metabolism of aromatic compounds, was investigated <em>in vitro</em> for its effect on HL fibrillation using spectroscopic, calorimetric, and computational methods. The results indicate that HA enhances HL fibrillation in a concentration-dependent manner, evidenced by increased ThT fluorescence and the detection of amyloid fibrils with a hydrodynamic radius of approximately 840.8 nm through dynamic light scattering and right-angle light scattering. Furthermore, HA promotes the conversion of HL's α+β structure into a predominantly β-sheet configuration, as confirmed by far-UV CD spectroscopy. This interaction occurs through the formation of a complex between HA and HL, stabilized by hydrogen bonds and hydrophobic interactions, as demonstrated by isothermal titration calorimetry (ITC) and computational studies. Specifically, HA binds to Q58 and N60 in the aggregation-prone region 2 (APR2) and Trp64 in non-aggregation-prone region, inducing conformational changes that favours fibrillation. The relative lytic activity of HL increase in presence of HA which further confirm the non-involvement of key residues, D35 and E53 in binding of HA to HL. Also, HL fibrils formed in presence of HA increases the hemolysis of RBCs and the appearance of more mis-shaped RBCs. Consequently, HA significantly enhances amyloid fibrillation in HL which provides valuable insights for future research focusing on <em>in vivo</em> studies, pre-clinical trials, and clinical applications.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110392"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of novel N-acridine thiosemicarbazones with lipid membrane: NMR and molecular dynamics simulations","authors":"Vladimir E. Koshman ,&nbsp;Alexey A. Dmitriev ,&nbsp;Viktor A. Timoshnikov ,&nbsp;Alina S. Arkhipova ,&nbsp;Olga Yu Selyutina ,&nbsp;Nikolay E. Polyakov","doi":"10.1016/j.abb.2025.110390","DOIUrl":"10.1016/j.abb.2025.110390","url":null,"abstract":"<div><div>NMR and molecular dynamics simulations revealed differences in the localization of the novel thiosemicarbazones: 2-benzoyl ((E)-N-(acridin-9-yl)-2-(phenyl(pyridin-2-yl)methylene)hydrazine-1-carbothioamide (AOBP) and 2-dipyridyl ((E)-N-(acridin-9-yl)-2-(di(pyridin-2-yl)methylene)hydrazine-1-carbothioamide (AODP) within the lipid membrane. It turned out that both thiosemicarbazones can penetrate inside the membrane, but AOBP is able to pass into the center of the hydrophobic region of the lipid bilayer, while AODP is distributed closer to the surface and freely leaves the membrane into the aqueous environment. The presence of cholesterol was also found to prevent both thiosemicarbazones from penetrating the membrane. The mechanism of anti-proliferative activity of some TSCs is related to the penetration through the lysosomal membrane and formation of cytotoxic copper complexes, which generate ROS resulting in lysosomal membrane permeabilization and cell death. Hydrophobic drugs, including TSCs, could penetrate through lysosomal membrane via passive diffusion, thus the affinity of drug to the hydrophobic interior of the lipid membrane could be important for their activity. Since the mechanism of thiosemicarbazones anticancer activity is associated with their penetration into lysosomes, the results obtained are important for a better understanding of the mechanisms of activity of these compounds and the development of new drug agents.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110390"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated circular RNA and long non-coding RNA-Mediated regulatory competing endogenous RNA networks (ceRNETs) in ovarian and cervical cancers: A non-coding RNA-Mediated mechanism of chemotherapeutic resistance with new emerging clinical capacities","authors":"Danial Amiri Manjili ,&nbsp;Fatemeh Naghdi Babaei ,&nbsp;Tayebeh Younesirad ,&nbsp;Sara Ghadir ,&nbsp;Hamid Askari ,&nbsp;Abdolreza Daraei","doi":"10.1016/j.abb.2025.110389","DOIUrl":"10.1016/j.abb.2025.110389","url":null,"abstract":"<div><div>Cervical cancer (CC) and ovarian cancer (OC) are among the most common gynecological cancers with significant mortality in women, and their incidence is increasing. In addition to the prominent role of the malignant aspect of these cancers in cancer-related women deaths, chemotherapy drug resistance is a major factor that contributes to their mortality and presents a clinical obstacle. Although the exact mechanisms behind the chemoresistance in these cancers has not been revealed, accumulating evidence points to the dysregulation of non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as key contributors. These ncRNAs perform the roles of regulators of signaling pathways linked to tumor formation and chemoresistance. Strong data from various recent studies have uncovered that the main mechanism of these ncRNAs in the induction of chemoresistance of CC and OC is done through a dysregulated miRNA sponge activity as competing endogenous RNA (ceRNA) in the competing endogenous RNA networks (ceRNETs), where a miRNA regulating a messenger RNA (mRNA) is trapped, thereby removing its inhibitory effect on the desired mRNA. Understanding these mechanisms is essential to enhancing treatment outcomes and managing the problem of drug resistance.</div><div>This review provides a comprehensive overview of lncRNA- and circRNA-mediated ceRNETs as the core process of chemoresistance against the commonly used chemotherapeutics, including cisplatin, paclitaxel, oxaliplatin, carboplatin, and docetaxel in CC and OC. Furthermore, we highlight the clinical potential of these ncRNAs serving as diagnostic indicators of chemotherapy responses and therapeutic targets.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110389"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}