Journal of physiology and biochemistry最新文献

{"title":"The multifaceted regulation of white adipose tissue browning and their therapeutic potential.","authors":"Abhishek Satheesan, Janardanan Kumar, Kakithakara Vajravelu Leela, Rahul Harikumar Lathakumari, Matcha Angelin, Ria Murugesan, Venkata Chaithanya","doi":"10.1007/s13105-025-01117-3","DOIUrl":"https://doi.org/10.1007/s13105-025-01117-3","url":null,"abstract":"<p><p>Adipose tissue browning, the conversion of white adipose tissue (WAT) into brown or beige adipose tissue, offers potential for combating obesity and metabolic disorders. This review delves in to the transcriptional and epigenetic regulation of WAT browning and how it impacts metabolic health and its significance in various disease conditions. Further the review explains how various external factors such as diet and exercise play an influential role in the regulation of WAT browning. UCP1 gene, which plays a crucial role in cellular thermogenesis is found to be the major mediator of this phenomenon along with functional dynamics of mitochondria. Gut microbiome has been another focus point in this review that highlights how alterations to the composition of different species of bacteria in gut microbiome can directly influence WAT browning. Finally the review discusses the various pharmaceutical and neutraceutical options under research that targets WAT browning to improve metabolic status of an individual. Therapeutic strategies include β3-adrenergic receptor agonists, GLP-1 receptor agonists, AMPK activators, and natural compounds such as capsaicin and resveratrol. Emerging CRISPR/Cas9 gene therapies aim to induce WAT browning. Clinical evidence to prove the significance of this phenomena is currently limited but growing rapidly as seen in the number of clinical trials that are undergoing currently, therefore the review strongly rely upon animal model and cell culture based studies to justify this area of novel research. Despite its potential, challenges like individual variability, long-term safety, and complex gut microbiome interactions remain. Future research should target novel pathways, optimize therapeutic regimens, and personalize treatments.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817019","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":"Alpha-ketoglutarate supplementation differently modifies hematological parameters and oxidative stress in mice fed a standard diet and high-fat high-fructose diet.","authors":"Myroslava V Vatashchuk, Viktoriia V Hurza, Oleksandra B Abrat, Maria P Lylyk, Khrystyna Matvieieva, Dmytro V Gospodaryov, Oleh I Demianchuk, Kenneth B Storey, Maria M Bayliak, Volodymyr I Lushchak","doi":"10.1007/s13105-025-01115-5","DOIUrl":"https://doi.org/10.1007/s13105-025-01115-5","url":null,"abstract":"<p><p>Long-term consumption of high-calorie diets can lead to metabolic disorders. In this study, we evaluated the effects of an eight-week standard (control), high-fat high-fructose (HFFD), alpha-ketoglutarate (AKG)-supplemented (1% in drinking water), and combined diet (HFFD + AKG) on hematological and oxidative stress parameters across tissues of male C57BL/6J mice. Both HFFD and AKG decreased erythrocyte count and altered leukocyte profile, increasing neutrophils and monocytes while decreasing lymphocytes. HFFD increased visceral fat mass and intensified oxidative stress in adipose tissue, as indicated by elevated lipid peroxide (LOOH) levels. LOOH levels in adipose tissue of AKG- and HFFD + AKG-fed mice matched control. HFFD or AKG lowered glutathione peroxidase and NAD(P)H-quinone oxidoreductase 1 (NQO1) activities in adipose tissue relative to control, unlike HFFD + AKG-fed counterparts. The heart showed an adaptive response to HFFD, with increased glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase, and NQO1 activities, and lower levels of oxidized glutathione (GSSG). AKG increased reduced glutathione (GSH) levels and elevated GPx and GST activities in the heart, whereas HFFD + AKG-fed mice had lower LOOH levels than HFFD-fed counterparts. Similarly, HFFD and AKG decreased GSSG and increased GSH in skeletal muscle. Both AKG- and HFFD + AKG-fed mice had lower carbonyl protein levels in muscle compared to control and HFFD-fed mice. Like adipose, muscle of HFFD- and AKG-fed mice had lower NQO1 activity compared to control, unlike HFFD + AKG group. These findings suggest AKG may mitigate HFFD-induced oxidative stress and modulate hematological parameters, with tissue- and diet-dependent effects, suggesting its role as an antioxidant under metabolic stress and a regulator of baseline redox homeostasis.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784582","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":"P4HA2 promotes the progression of thyroid cancer by regulating PFKP-mediated glycolysis.","authors":"Jingfu Sun, Qing Zhu, Liqun Shan, Jianing Liu","doi":"10.1007/s13105-025-01114-6","DOIUrl":"https://doi.org/10.1007/s13105-025-01114-6","url":null,"abstract":"<p><p>Emerging evidence suggests that prolyl-4-hydroxylase α subunit 2 (P4HA2) plays critical roles in cancer progression through multiple mechanisms. Notably, P4HA2 has been implicated in modulating glycolytic pathways in malignancies. Phosphofructokinase (PFKP), a key glycolytic enzyme, exhibits significant overexpression in thyroid cancer. This study investigates the functional of P4HA2 in thyroid cancer and elucidates the P4HA2/PFKP axis in regulating cancer cell glycolysis. Bioinformatics analysis using GEPIA website revealed P4HA2 expression patterns in thyroid cancer samples. P4HA2 protein levels were detected in thyroid cancer cell lines by western blot assay. Functional characterization was performed through siRNA-mediated P4HA2 knockdown followed by evaluation of proliferative capacity, cell cycle progression, migratory/invasive potential, and glycolytic activity. Rescue experiments employing PFKP overexpression were conducted to delineate molecular interactions. Significant P4HA2 up-regulation was observed in thyroid cancer tissues and cell lines. P4HA2 silencing marked inhibited cellular proliferation, suppressed cell cycle regulators, and attenuated metastatic potential. Glycolytic parameters including glucose consumption, lactate production, and ATP synthesis were significantly compromised following P4HA2 knockdown. Mechanistically, P4HA2 depletion down-regulated PFKP expression, while PFKP overexpression partially rescued the oncogenic phenotype. Our data indicated that P4HA2 promoted cell proliferation, cell cycle, migration, invasion, glycolysis and tumor growth, suggesting that it might be a valuable therapeutic target for thyroid cancer.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784583","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":"Sirtuin 1 overexpression in mice preserves insulin and thermogenic responses in subcutaneous inguinal white adipose tissue under proinflammatory conditions.","authors":"Patricia Vázquez, Carmen Escalona-Garrido, Nuria Pescador, Ana B Hitos, Daniel González-Moreno, Ángela de Benito-Bueno, Elena Sierra-Filardi, Patricia Boya, Ana Montero-Pedrazuela, Ana Guadaño-Ferraz, Ángela M Valverde","doi":"10.1007/s13105-025-01109-3","DOIUrl":"https://doi.org/10.1007/s13105-025-01109-3","url":null,"abstract":"<p><p>Activation of brown adipose tissue (BAT) or subcutaneous adipose tissue (iWAT in mice) is a strategy to regulate metabolic homeostasis. The NAD⁺-dependent deacetylase Sirtuin 1 (SIRT1) plays an essential role in energy metabolism and inflammation and is a promising target to tackle obesity and associated comorbidities. We have previously reported the beneficial effect of moderate SIRT1 overexpression in protecting mice against inflammation-induced insulin resistance and impaired BAT thermogenesis. Here, we investigated the effect of an inflammatory environment on insulin sensitivity and thermogenic capacity in iWAT from wild-type (WT) or SIRT1 overexpressing mice (Sirt1^Tg+). We also analyzed in vitro responses to insulin and norepinephrine (NE) in subcutaneous white adipocytes (iWA) from both genotypes under proinflammatory conditions. Results showed higher UCP-1 levels in iWAT from Sirt1^Tg+ mice under thermoneutral conditions compared to WT mice, an effect also found in vitro in differentiated iWA. Cold-induced UCP-1 expression and insulin-induced Akt phosphorylation levels were reduced in iWAT from WT mice upon in vivo bacterial lipopolysaccharide (LPS) injection. However, these reductions were attenuated in iWAT from Sirt1^Tg+ mice. Likewise, in iWA exposed to the conditioned medium from LPS-stimulated Raw 264.7 macrophages (CM-LPS) both insulin signaling and NE-induced UCP-1 expression levels were preserved only in cells overexpressing SIRT1. LPS or CM-LPS increased SIRT1 levels in iWAT or iWA, respectively, an effect more evident upon SIRT1 overexpression. Collectively, our results suggest a SIRT1-dependent anti-inflammatory compensatory response that likely protects iWAT from the deleterious effects of inflammation.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784584","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":"Hedgehog signaling pathway is an influential factor on vascular biology: a review.","authors":"Mi Ai, Li Xiao, Yilin Yu, Laidi Wu, Ollie Yiru Yu, Yingguang Cao, Jianmiao Liu, Ke Song","doi":"10.1007/s13105-025-01113-7","DOIUrl":"https://doi.org/10.1007/s13105-025-01113-7","url":null,"abstract":"<p><p>Hedgehog (Hh) signaling is an important pathway involved in major biological processes such as embryonic development, adult morphogenesis, and vascular biology (i.e., vasculogenesis, angiogenesis and arterial remodeling). The latter role was more recently elucidated, occurring through regulation of angiogenic cytokines and controlling the proliferation, and migration of endothelial cells (ECs) or vascular smooth muscle cells (VSMCs), that help deliver oxygen and nutrients to tissues. Anomalous inhibition or activation of Hh signaling is therefore implicated in various pathological conditions, including vascular diseases. However, the mechanisms of Hh involvement in vascular biology have not been systematically clarified. This review covers recent research regarding the regulatory role and mechanism of Hh signaling in vasculogenesis, angiogenesis, and arterial remodeling. We conclude that the Hh signaling pathway holds great promise for treating vascular diseases and cancers. We encourage further research to develop a full understanding of the underlying mechanisms so that we can better determine the Hh pathway's therapeutic value.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765036","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":"Curcumin ameliorates hepatic steatosis and insulin resistance through the JNK2/FOXO1/Bcl6 axis and regulate the intestinal flora structure.","authors":"Ju Yang, Biaozhang Song, Feng Zhang, Bing Liu, Jiai Yan, Yingyu Wang, Jing Sun, Chengguang Zhao, Dan Li, Hong Cao","doi":"10.1007/s13105-025-01101-x","DOIUrl":"10.1007/s13105-025-01101-x","url":null,"abstract":"<p><p>Curcumin, a polyphenol extracted from the plant turmeric rhizoma, is well known for its strong antioxidant capacity and beneficial effects on the treatment of obesity induced by a high-fat diet in mice. However, the exact mechanism of action by which it improves obesity remains elusive. The aim of this study was to investigate the effect of curcumin on the biological phenotype of HFD-induced obese mice, to determine the related metabolic pathways and to determine whether the intestinal flora is involved. C57BL/6 mice were fed HFD for 8 weeks and then gavaged with 200 mg/kg curcumin or the same volume of vehicle for 16 weeks. The body weight, blood glucose level, blood lipid level, insulin resistance and oxidative stress level of the mice were detected to determine the effect of the treatment on lipid metabolism. Liver transcriptome analysis combined with qPCR and cell experiments revealed that curcumin improves hepatic steatosis and insulin resistance in mice fed a high-fat diet by downregulating the JNK2/FOXO1/Bcl6 axis. Curcumin treatment can regulate the composition and structure of intestinal flora in high-fat diet-fed mice, and increase the relative abundance of beneficial bacteria such as Coriobacteriaceae, Mailhella, Faecalibaculum, Phocaeicola vulgatus, Parvibacter vulgatus, and Bacteroides intestinalis, which are associated with obesity and metabolic disorders, while reducing the relative abundance of harmful bacteria such as Alistipes, Oscillibacter, Lactobacillus johnsonii, and Acutalibacter muris. In conclusion, curcumin ameliorated hepatic steatosis and insulin resistance in HFD-fed mice by down-regulating hepatic JNK2/FOXO1/Bcl6 axis and altering the composition and structure of intestinal flora.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"771-791"},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540639","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":"Nuclear magnetic resonance-based metabolomic study of rat brain after different intensity treadmill running.","authors":"Ni Zeng, Jie-Ting Li, Zhi-Juan Zhang, Zhi-Peng Yan, Tao Liao, Guo-Xin Ni","doi":"10.1007/s13105-025-01094-7","DOIUrl":"10.1007/s13105-025-01094-7","url":null,"abstract":"<p><p>Previous studies have revealed that different intensities of exercise training have an impact on cognition. However, the cognitive effects of different intensities of exercise and its underlying mechanisms are not fully understood. The aim of this paper was to investigate the effects of different intensities of treadmill exercise on cognition in rats from the perspective of metabolomic analysis. In this study, ninety-six male rats were randomly divided into four groups: control group (CON group, n = 24), low-intensity running group (LIR group, n = 24), medium-intensity running group (MIR group, n = 24), and high-intensity running group (HIR group, n = 24). After 4 weeks of treadmill running, rats in the LIR group located the platform significantly faster than those in the CON(p = 0.027) and HIR(p = 0.011) groups. After 8 weeks of treadmill running, rats in the LIR and MIR groups also found the platform more quickly than those in CON group (p = 0.003 and p = 0.015, respectively). Additionally, rats in the MIR group showed significantly increased superoxide dismutase (SOD)/catalase (CAT) in the hippocampus compared with those exposed to HIR(p = 0.03), LIR(p = 0.0008), and CON(p = 0.0004). Metabolomic analysis revealed that, after 8 weeks of running, 14 metabolites with similar characteristics differed between the MIR and HIR groups compared to the CON group. The LIR group showed significant alterations in 12 key metabolites compared to the CON group. The LIR, MIR, and HIR groups also demonstrated significant changes in 3, 4, and 3 metabolic pathways respectively, when compared to the CON group. In conclusion, the above results indicate that LIR can effectively decrease fumarate accumulation, thereby enhancing the TCA cycle and brain energy metabolism which in turn improved cognitive function, while MIR can modify glutathione metabolism to alleviate oxidative stress (OS), supporting cognitive function.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"687-697"},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136278","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":"The importance of vitamin D levels in patients with inflammatory bowel disease.","authors":"Evgenia Koureta, Pantelis Karatzas, Panagiotis Kanellopoulos, Angeliki Papapanagiotou, Vasileios Lekakis, Giorgos Bamias, Andreas Koutsoumpas, George Karamanolis, Jiannis Vlachogiannakos, Athanasios G Papavassiliou, George V Papatheodoridis","doi":"10.1007/s13105-025-01096-5","DOIUrl":"10.1007/s13105-025-01096-5","url":null,"abstract":"<p><p>The possible role of vitamin D (VD) in the pathogenesis of inflammatory bowel disease (IBD) and the associations between VD levels and IBD activity remain unclarified. We aimed to assess VD levels in IBD patients and their associations with IBD activity. We evaluated VD levels in Greek patients aged 18-75 years old with Crohn's disease (CD) or ulcerative colitis (UC). Patients were ineligible under the following conditions: history of enterectomy/right colectomy, receiving VD or agent(s) interfering with VD metabolism during the last three months and any comorbidities that influence VD levels. Epidemiologic characteristics, clinical course, laboratory investigations, endoscopic and histologic findings were recorded. In total, 122 patients with CD and 71 with UC were included. Most of them had low levels of VD (90% of CD and 91.5% of UC patients). Patients with clinically active CD or UC had lower levels of VD compared to those in remission (p = 0.009 and p = 0.033, respectively).CD patients with low levels of VD had higher CRP and stool calprotectin compared to those with normal levels of VD (P = 0.032 and P = 0.002, respectively). In UC, patients with pancolitis had lower VD levels compared to patients with proctitis (P = 0.036). In conclusion, the majority of Greek IBD patients have low levels of VD. Clinical activity is related to lower levels of VD. Low compared to normal levels of VD in CD patients are associated with higher CRP and calprotectin levels, so VD levels might serve as an activity marker.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"729-739"},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142823","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":"Spexin peptide ameliorates renal injury in diabetic nephropathy rat model via modulation of metabolic, oxidative, inflammatory, and apoptotic dysregulations.","authors":"Hadeel Elsherbiny, Sulaiman Mohammed Alnasser, Mohamed Aref, Esraa ElSheikh, Sherein F El-Sayed, Nanees F El-Malkey, Haifa A Alqahtani, Abdullah A A Alghamdi, Mohamed A Nassan, Hanan H Abd-ELhafeez, Gamal A Salem","doi":"10.1007/s13105-025-01092-9","DOIUrl":"10.1007/s13105-025-01092-9","url":null,"abstract":"<p><p>Diabetic nephropathy is recognized as the predominant cause of end-stage renal disease worldwide. In reaction to metabolic stress, the peptide hormone spexin-14, is synthesized in both central and peripheral tissues. Its level is reduced in type II diabetes mellites and may play a role in glucose metabolism. However, in the context of DN, the mechanisms through which spexin exerts its effects remain largely unknown. This research employed a rat model of DN to explore the therapeutic potential and the underlying mechanisms associated with spexin treatment. For the development of this experimental model, rats were subjected to an eight-week regimen of a high-fat, high-fructose diet prior to receiving a single dose of streptozotocin (35 mg/kg body weight). Subsequently, spexin was administered subcutaneously on a daily basis for a duration of eight weeks at a dosage of 50 µg/kg body weight. The evaluation methods employed encompassed renal function assessments, macromorphological examinations, histopathological evaluations, and analyses of inflammatory and oxidative stress mediators. Additionally, immunohistochemical staining for NF-kB and E-cadherin, along with PCR analysis of mTOR, Bcl2, and Bax gene expressions in renal tissues, were conducted. Following the administration of spexin to the diabetic rats, there was a significant reduction in serum levels of glucose, urea, creatinine, and inflammatory cytokines (IL-1β, TNF-α), alongside a marked restoration of antioxidant enzyme activities. Furthermore, a significant decline in the levels of NF-κB, mTOR, and Bax was noted and accompanied with increased expressions of Bcl-2 and E-cadherin proteins. The observed improvements in histopathological changes significantly corroborated the biochemical results. In summary, spexin has proven to be effective in alleviating DN by its capacity to mitigate metabolic disturbances, oxidative stress, inflammation, and apoptosis.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"657-672"},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136281","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":"m6A-modified circCCAR1 promotes malignant proliferation by enhancing KIF5B expression in hepatocellular carcinoma.","authors":"Jiayu Chen, Zhuolin Zhou, Yang Shen, Xinyao Hu, Yukai Chen, Le Xu, Ling Wang, Junhua Li, Ximing Xu","doi":"10.1007/s13105-025-01112-8","DOIUrl":"10.1007/s13105-025-01112-8","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is known for its aggressive nature and high mortality rates. Circular RNAs (circRNAs) have emerged as critical regulators of cancer progression, yet the role of the circRNA cell division cycle and apoptosis regulator 1 (circCCAR1) in HCC is poorly understood. This study aims to explore the mechanism of circCCAR1 in HCC progression. We measured the expression of circCCAR1, miR-641, and motor protein kinesin family member 5B (KIF5B) in HCC cell lines and normal hepatic cells, revealing that circCCAR1 was significantly overexpressed in HCC. Mechanistic analyses showed that the RNA methyltransferase YTH domain-containing protein 1 (YTHDC1) recognized N6-methyladenosine (m6A) modifications on circCCAR1, facilitating its transport from the nucleus to the cytoplasm. In the cytoplasm, circCCAR1 acted as a molecular sponge to sequester miR-641, relieving miR-641-mediated inhibition of KIF5B mRNA. CircCCAR1 directly bound to the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), which stabilized KIF5B mRNA. Functional experiments demonstrated that silencing circCCAR1 suppressed HCC cell proliferation, induced apoptosis, and reduced tumor growth in a xenograft mouse model, effects that were partially reversed after KIF5B overexpression or miR-641 inhibition. In conclusion, YTHDC1 promotes the cytoplasmic translocation of m6A-modified circCCAR1 and circCCAR1 facilitates HCC progression through the miR-641/KIF5B axis.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"815-829"},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690588","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}