Wnt Expression Research Articles

Age-related renal impairment often occurs insidiously and has become an important cause of chronic renal failure, especially when individuals with other chronic diseases. However, there is lack of effective treatments. Research on diabetic patients has revealed that empagliflozin (EMPA), one of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, exhibits a distinct protective effect on aging kidneys. EMPA has been shown to improve renal fibrosis and ameliorate inflammatory cytokines, including IL-1 and IL-8, which are closely associated with the aging process in db/db mouse models. As a result, we assessed markers indicative of kidney senescence P16 and senescence-associated β-galactosidase (SA-β-gal) in the renal tissue of male C57 mice undergoing natural aging, following treatment with EMPA. Our findings showed that in Old-EMPA group, the expression of P16 and SA-β-gal were downregulated compared to Old-vehicle group, while these markers were expressed lower in Young group. RNA sequencing analysis indicated that our findings correlated with increased expressions of Six1 and Wnt4 in the kidney. Protein-protein interaction (PPI) analysis confirmed an interaction between Six1 and Wnt4. After treatment with EMPA,the expression of Six1 and Wnt4 was observed to increase in both aging Primary renal tubular epithelial cells (PRTECs) and HK-2 cells, whereas the expression of NF-κB and its downstream effectors IL-1β and TNF-α decreased, leading to an improvement in aging-related changes.

ABSTRACTPlanarian muscle produces key wound signal patterning whole-body regeneration. Within muscle, generic induction of wnt1 promotes tail regeneration, while polarized expression of the Wnt inhibitor notum at anterior-facing wounds drives head regeneration. Classic experiments indicate that microtubules are also involved in blastema fating, but the cell biology of planarian muscle is still poorly understood. We raised an antibody to muscle-expressed TUBA-2 and found that planarian muscle possesses a microtubule network linking contractile fibers with their mononucleated cell bodies. Microtubules were required for muscle fiber regrowth across wound sites at times that correlated with expression of wound-induced genes. Expression profiling found that sublethal colchicine treatment disrupted a subset of muscle-expressed injury-induced genes, with strongest effects on wnt1 and notum. Higher colchicine doses (>200 µg/ml) prevented wnt1 and notum expression, while, surprisingly, lower doses (125 µg/ml) elevated notum at posterior-facing wounds, thereby implicating microtubules in both the activation and polarization of genes expressed from injured muscle. Furthermore, microtubules functionally interact with Wnts to control head/tail determination. Together, planarian microtubules act in specific regulatory pathways to express key muscle-expressed and injury-induced factors used for blastema fating.

To observe the effects of ultrasound-guided foraminal electroacupuncture on neuronal apoptosis and motor function in rats with spinal cord injury (SCI), and to explore the potential underlying mechanisms. Thirty-six SPF-grade Sprague-Dawley rats were randomly assigned to a sham operation group, a model group, and an ultrasound-guilded electroacupuncture group (electroacupuncture group), with 12 rats in each group. In the sham operation group, the spinal cord was exposed and then the incision was sutured without contusion. In the other two groups, SCI models were established using a modified Allen's impact method. On days 1, 3, 7, and 14 after modeling, the electroacupuncture group received electroacupuncture intervention at the T9/T10 and T10/T11 intervertebral foramen under ultrasound guidance, avoiding spinal cord injury. Stimulation parameters were dense-disperse wave at 2 Hz/100 Hz and 1-2 mA for each session. Following interventions on days 1, 3, 7, and 14, the Basso-Beattie-Bresnahan (BBB) score was assessed; the inclined plane test was used to assess hindlimb grip strength in rats. After the intervention, HE staining was used to observe spinal cord morphology; TUNEL staining was used to detect neuronal apoptosis; ELISA was used to measure the serum levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α); Western blot was used to analyze the protein expression of Wnt-4, β-catenin, c-Myc, Bax, Bcl-2, and NeuN in spinal tissue; quantitative real-time PCR was used to detect the mRNA expression of Wnt-4, β-catenin, c-Myc, Bax, Bcl-2, and NeuN. Compared with the sham operation group, the model group showed significantly reduced BBB scores (P<0.05), and reduced inclined plane angles (P<0.05) at all time points. Compared with the model group, the electroacupuncture group exhibited increased BBB scores on days 3, 7, and 14 (P<0.05), and higher inclined plane angles on days 1, 3, 7, and 14 (P<0.05). Compared with the sham operation group, the model group showed disorganized spinal cord structure with increased inflammatory cells and necrotic neurons, higher number of apoptotic neurons in spinal tissue (P<0.05), elevated serum IL-6, IL-1β, and TNF-α levels (P<0.05), increased protein and mRNA expression of Wnt-4, β-catenin, c-Myc, and Bax (P<0.05), and decreased protein and mRNA expression of Bcl-2 and NeuN in spinal tissue (P<0.05). Compared with the model group, the electroacupuncture group had fewer inflammatory cells and apoptotic neurons in spinal tissue (P<0.05), reduced serum IL-6, IL-1β, and TNF-α levels (P<0.05), increased protein and mRNA expression of Wnt-4, β-catenin, Bcl-2, and NeuN (P<0.05), and decreased protein and mRNA expression of c-Myc and Bax in spinal tissue (P<0.05). Ultrasound-guided foraminal electroacupuncture could improve motor function in rats with SCI, potentially by regulating the expression of molecules related to the Wnt-4/β-catenin signaling pathway to inhibit neuronal apoptosis and inflammatory responses.

FZD7 is one of the key players in the subset of WNT-TGFβ-activated hepatocellular carcinomas (HCC), but the consequences of its abnormal expression on hepatocarcinogenesis remain to be better understood. Herein, we aimed to investigate the role of the FZD7-mediated signaling in immature phenotype and aggressiveness of HCC. Firstly, 499 human HCCs were used for clinical and molecular comparisons regarding the expression of FZD7 and stemness-associated markers. We showed that FZD7 overexpression was associated with poor differentiation and, in combination with CD133, predicted a poor outcome of patients with aggressive recurrence. Next, the impact of WNT3/FZD7 signaling on the differentiation of hepatic cells was assessed in HCC cell lines, as well in the non-transformed progenitor HepaRG cell line and in primary human hepatocytes, transduced with WNT3 and FZD7-expressing lentiviruses. We demonstrated that the ectopic expression of WNT3 and FZD7 inhibited the differentiation behavior of HepaRG cells and human primary hepatocytes, amplified the pool of EpCAM(+), CD90(+) and CD133(+) subsets of HCC cell lines, and increased their cancer stem cell features. Moreover, we found that WNT3/FZD7-mediated stemness properties of cancer cells were independent of the stemness-associated marker NANOG. In conclusion, we identified the FZD7(+)/CD133(+) signature as a potential prognosis marker and molecular therapeutic target, and we strengthened the hypothesis for the involvement of FZD7 in the enrichment of a cancer stem cell pool in HCC.

BACKGROUNDThe therapeutic potential of induced pluripotent stem cells (iPSCs) for Parkinson’s disease (PD) has been demonstrated. Exercise can also modulate metabolism to improve motor dysfunction in PD patients.AIMTo investigate the therapeutic effect of exercise combined with iPSCs in a PD mouse model and explore the underlying mechanisms.METHODSIn this study, we included 10 normal mice and 40 PD model mice, which were divided into five groups: The control group (n = 10), the sedentary PD group (St group, n = 10), the exercise PD group (E group, n = 10), the iPSC-treated PD group (T group, n = 10), and the combined exercise and iPSC-treated PD group (ET group, n = 10). The T and ET groups received cell injection therapy, while the E and ET groups underwent an 8-week exercise intervention. After the intervention, behavioral tests were performed on mice from all groups. Serum levels of epinephrine (EPI) and nerve growth factor were measured, and the expression of Wnt1, Lmx1a, and other factors related to the Wnt signaling pathway in the midbrain of mice were assessed.RESULTSThe motor ability of the T group was higher than that of the St group, but the difference was not significant. However, the protein and gene expression levels of Wnt1, Lmx1a, Neurog2, and TH in the T group were significantly higher than those in the St group (P < 0.01). Compared with the T group, the motor ability of the E group was significantly enhanced (P < 0.01), and the gene expression level of Wnt1 in the midbrain of the E group was significantly higher than that of the T group (P < 0.05). The levels of EPI and nerve growth factor were increased in both the E and ET groups. Exercise can improve motor dysfunction in PD, increase EPI levels, and elevate Wnt1 levels. However, western blot results revealed no significant change in the TH level of the E group, which may be because exercise does not cause a noticeable change in the number of neurons. Compared with the St group, both the E and ET groups showed improved motor function (P < 0.01). The results showed that compared with the St group, the protein and gene expression levels of Wnt1, Lmx1a, and Neurog2 were significantly increased in the E, T, and ET groups (P < 0.05). Compared with the T and E groups, the protein and gene expression levels of Wnt1, Lmx1a, and Neurog2 were significantly increased in the ET group (P < 0.05).CONCLUSIONExercise increases EPI levels, activates the Wnt signaling pathway through β2 receptors, enhances the Wnt1-Lmx1a regulatory loop, and promotes the differentiation of iPSCs into dopaminergic neurons, thereby increasing the number of neurons.

Retinoblastoma (RB) is a common intraocular malignant tumor affecting infants and children, yet its precise etiology and pathogenesis remain incompletely understood. Curcumin, a bioactive polyphenol, inhibits tumor progression via microRNA-mediated modulation of the Wnt/β-catenin signaling cascade. This study aimed to clarify how curcumin mediates its antitumor effects in RB by investigating its regulation of miRNA-22 (miR-22) expression and exploring the underlying molecular mechanisms. Two validated retinoblastoma models (SO-RB50/WERI-Rb-1) were treated with curcumin at varying concentrations. To delineate miR-22's regulation of Wnt/β-catenin signaling, target cells were transduced with either a miR-22 mimic lentivirus or a non-functional control lentivirus. Xenograft tumor models were established in mice using human RB cells to observe the in vivo effects of curcumin on tumor size, miR-22 expression, and Wnt/β-catenin protein levels. Cellular proliferation, invasion, and apoptosis were assessed using the CCK-8, Transwell, and Annexin V-APC-PI dual staining assay, respectively. miR-22 levels were quantified by RT-PCR, and Wnt1 and β-catenin expression profiles were determined by Western blot analysis. Curcumin treatment resulted in decreased proliferation and invasiveness in RB cells, while enhancing apoptosis and elevating miR-22 expression. Inhibition of miR-22 diminished curcumin's effects on the Wnt/β-catenin signaling pathway. In xenograft studies, curcumin significantly reduced tumor size and enhanced miR-22 expression within the tumors, effectively suppressing Wnt/β-catenin signaling. These findings demonstrate that curcumin inhibits RB cell proliferation and invasiveness while promoting apoptosis, primarily mediated through miR-22 upregulation and subsequent inhibition of the Wnt/β-catenin pathway.

A spatiotemporal atlas of orchiectomy-induced androgen deprivation-mediated modulation of cellular composition and gene expression in the mouse prostate

IL-33 links inflammation and bone remodeling in experimental spondyloarthritis and human joint biopsies.

Different effects of tumor necrosis factor monoclonal antibody and receptor fusion protein on bone metabolism.

TSPEAR S475TfsX79 mutation does not affect auditory function, tooth morphology or hair development in mice.

BackgroundAcute kidney injury (AKI) results from cisplatin chemotherapeutic agents in 30 %–46 % of patients, but clinically effective preventive and therapeutic approaches are lacking. Bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exo) have potential in tissue repair, but the mechanism by which they attenuate cisplatin-induced kidney injury is unknown.ObjectiveTo explore the therapeutic effect of BMSCs-exo on cisplatin-induced AKI and to analyze the key molecular mechanism involved.Methods and materialsBMSCs-exo were extracted via ultracentrifugation and identified via transmission electron microscopy, nanoparticle analysis and Western blot. C57BL/6 mice were divided into a control group (Con), a cisplatin model group (Cis), and a BMSCs-exo treatment group (BMSCs-exo), and renal function was dynamically tested. PAS staining was used to observe histopathological changes in mouse kidney tissues, while immunohistochemistry was employed to assess the expression levels of Wnt4, β-catenin, FZD5, CD31, and the tubular injury markers NGAL and KIM1. Western blot was used to detect the expression of Wnt4, β-catenin, FZD5 and CD31. High-throughput sequencing was used to screen for differential miRNAs, and GO/KEGG enrichment analysis of target genes was performed.ResultsBlood creatinine and urea nitrogen levels were significantly higher in the Cis group than in the Con group, and renal tubular epithelial cells exhibited necrosis, confirming successful AKI model establishment. BMSCs-exo alleviated renal dysfunction, histopathological alterations, and tubular injury in vivo, as evidenced by NGAL and KIM1 expression. We further demonstrated that BMSCs-exo specifically localized to the injured kidney. MiRNA sequencing of renal tissues from the Con, Cis and BMSCs-exo groups identified mmu-miR-874-3p—enriched in Wnt signaling and angiogenesis pathways—as a key mediator of the renoprotective effects of BMSCs-exo, with FZD5 as its downstream target. Moreover, treatment with BMSCs-exo markedly prevented microvascular loss. In the BMSCs-exo group, Wnt4, β-catenin and CD31 expression were upregulated, whereas FZD5 expression was downregulated, consistent with the immunohistochemistry results.ConclusionsBMSCs-exo protect kidneys against cisplatin-induced AKI(Cis-AKI) by attenuating injury to the renal microvasculature and tubule epithelial cells, primarily through mmu-miR-874-3p-mediated inhibition of FZD5 activation and promotion of Wnt/β-catenin pathway activation.

Metabolic, skeletal, and cartilage effects of a high-fat diet and the therapeutic impact of MGL3196 are age- and sex-dependent in mice.

Background/Objectives: Androgenetic alopecia suppresses hair follicle growth. This occurs via dihydrotestosterone (DHT), which inhibits key molecular pathways such as Wnt/β-catenin and Sonic Hedgehog (SHH) signaling. Exosomes derived from plant callus cultures are promising biomaterials for targeted delivery and regenerative medicine. This study aimed to investigate the protective effects of hemp seed callus-derived exosomes (E40) against DHT-induced inhibition of feather follicle development in a chicken embryo model. Methods: E40 exosomes were isolated and purified from the calli of germinated hemp seeds. A DHT-induced feather loss model was established by injecting chicken embryos on embryonic day 7 (E7) with DHT (50 ng/mL), with or without co-administration of E40 (40 µg/mL). On embryonic day 12 (E12), feather length, density, and expression of molecular markers were analyzed. The methods included FISH, Western blotting, and quantitative analysis of PTCH1, AR, SHH, SMO, GLI1, Wnt, β-catenin, BMP4, and Noggin. Results: DHT treatment significantly reduced feather length and density. It also downregulated SHH and Wnt/β-catenin markers, upregulating BMP4 and androgen receptor expression. Co-treatment with E40 restored feather length and density to levels comparable to controls and significantly recovered the expression of SHH, SMO, GLI1, Wnt, and β-catenin. E40 also suppressed DHT-induced BMP4 upregulation by approximately 30% and reduced androgen receptor expression. Conclusions: These results suggest that hemp seed-derived exosomes (E40) effectively mitigate DHT-induced feather follicle inhibition by modulating critical signaling pathways and immune-related markers, supporting their potential application as a nanocarrier-based therapeutic strategy for alopecia management.

Androgen deprivation therapy (ADT) remains a cornerstone in the treatment of prostate cancer (PCa), yet most tumors eventually develop resistance. Murine models are widely used to study PCa progression and ADT response, but a detailed understanding of the prostate’s biological response to androgen deprivation in these models is lacking. Here, we present a comprehensive spatiotemporal analysis of cellular and transcriptional dynamics in the mouse prostate following orchiectomy (ORX)-induced androgen deprivation. We observed progressive involution across all prostate lobes (dorsal, ventral, lateral, and anterior) and distinct lobe-specific temporal gene expression changes post-ORX. Immune cell infiltration markedly increased over time, highlighting a shift in the prostate’s cellular landscape. Single-cell RNA sequencing uncovered a previously undescribed fibroblast subtype—termed ORX-induced fibroblast (OIF)—characterized by high expression of Wnt2, Rorb, and Wif1, with distinct spatial localization. Pathway analysis revealed upregulation of amide and peptide binding functions, alongside suppression of peptidase and endopeptidase activity. Furthermore, dynamic changes in ligand–receptor interactions across lobes underscored the evolving intercellular communication in the post-ORX prostate. By integrating spatial transcriptomics with single-cell profiling, our study generates a high-resolution atlas of the murine prostate’s response to androgen deprivation. These findings provide a foundational resource for interpreting ADT responses in preclinical models of PCa.

The aim of this study is to investigate the physiological characteristics and regulatory mechanisms of porcine intramuscular fat (IMF), subcutaneous fat (take back fat (BF), for example), and visceral fat (take perienteric fat (PF), for example) to address the challenge of optimizing meat quality without excessive fat deposition. Many improved breed pigs have fast growth rates, high lean meat rates, and low subcutaneous fat deposits, but they also have low IMF content, resulting in poor meat quality. There is usually a positive correlation between intramuscular fat and subcutaneous fat deposits. This study selected eight-month-old female Tibetan pigs as experimental subjects. After slaughter, fat samples were collected. Histological differences in adipocyte morphology were observed via hematoxylin-eosin (HE) staining of tissue sections, and phenotypic characteristics of different adipose tissues were analyzed through fatty acid composition determination. Transcriptome sequencing and untargeted metabolomics were employed to perform pairwise comparisons between different fatty tissues to identify differentially expressed genes and metabolites. A siRNA interference model was constructed and combined with Oil Red O staining and lipid droplet optical density measurement to investigate the regulatory role of WNT16 in adipocyte differentiation. Comparative analysis of phenotypic and fatty acid composition differences in adipocytes from different locations revealed that IMF adipocytes have significantly smaller areas and diameters compared to other fat depots and contain higher levels of monounsaturated fatty acids. Integrated transcriptomic and metabolomic analyses identified differential expression of WNT16 and L-tyrosine, both of which are involved in the melanogenesis pathway. Functional validation showed that inhibiting WNT16 in porcine preadipocytes downregulated adipogenic regulators and reduced lipid droplet accumulation. This cross-level regulatory mechanism of "phenotype detection-multi-omics analysis-gene function research" highlighted WNT16 as a potential key regulator of site-specific fat deposition, providing new molecular targets for optimizing meat quality through nutritional regulation and genetic modification.

YAP1 signaling is essential for development but its specific roles in early embryogenesis remain poorly understood. To shed light on this, we analyzed YAP1’s role in regulating the pluripotency of the mammalian epiblast, using scRNAseq approaches. Conditional deletion of Yap1 in the mouse epiblast (Sox2-Cre) altered the expression of signaling genes, including Nodal, Wnt3, and Fgf8. Accordingly, Yap1 loss led to enhanced differentiation of the epiblast toward primitive streak lineages, as evidenced by the upregulation of T/Brachyury and Eomes genes. Furthermore, a proximity labeling assay in human pluripotent stem cells, followed by biochemical assays and molecular modeling predictions, revealed that YAP1 cooperates with QSER1 protein to regulate lineage genes. Our analysis shows that YAP1:TEAD4 enhancers recruit QSER1 to prevent RNA Polymerase II recruitment. Accordingly, QSER1 depletion, similar to YAP1, increases NODAL gene expression and leads to hyperactive NODAL signaling in human 2D-gastruloids. Overall, our findings define a role of YAP1 in the epiblast in vivo and uncovered an interplay with QSER1 controlling the activity of developmental signaling pathways in pluripotent cells.

Focal segmental glomerular sclerosis (FSGS) is considered an irreversible lesion in kidney disease. Here, we investigated the role of the wnt4/β-Catenin signaling pathway in FSGS lesion formation and the crosstalk between PECs and podocytes in a transgenic FSGS rat model and human primary FSGS to explore potential sex-specific differences and therapeutic options. After model induction in rats, we observed strong podocytes loss on day 7, which was significantly higher in male than in female rats. Starting at d14, both glomerular mRNA and protein expression of Wnt4 were increased, but more pronounced in males. Wnt4 was localized to podocytes and β-Catenin to Pax8-positive lesions. The Wnt4 target gene CD44 was strongly upregulated on d7 and increased until the end of the experiment (d42). In cell culture, we confirmed that injured podocytes expressed and secreted Wnt4, which stimulated the expression of the Wnt target gene Axin2 in PECs but not in podocytes. Wnt4/β-Catenin pathway activation was confirmed in human biopsies with podocytopathic FSGS. In conclusion, the canonical Wnt/β-Catenin axis plays a critical role in the crosstalk between PECs and injured podocytes. Furthermore, sex-specific differences in podocyte injury and regeneration appear to be, at least in part, Wnt4-mediated.

The development of craniofacial bones and teeth relies heavily on the Wnt signaling pathway, yet the specific mechanisms and Wnt variants involved remain under continual investigation. Using publicly available single-cell sequencing data from the mouse incisor, we reveal Wnt1 expression across dental structures and investigate its role using a Col1a1-dependent Wnt1 transgenic mouse model. Inducing Wnt1 early on affects craniofacial bone without disturbing tooth development, but prolonged embryonic induction leads to postnatal mortality with osteopetrosis-like bone overgrowth and malformed teeth. While tooth formation was initially unaffected by postnatal Wnt1 induction, prolonged activation impaired tooth root formation and odontoblast differentiation, resulting in shortened roots and thinner dentin. Three-dimensional micro-computed tomography quantification reveal that both embryonic and postnatal activation of Wnt1 significantly increase neural crest-derived craniofacial bone volume, whereas mesenchymal-derived craniofacial bones are unaffected. Importantly, osteoclastogenesis is suppressed by Wnt1 in a dose-dependent manner, revealed through bulk RNA sequencing and in vitro experiments. These findings emphasize the differential effects of Wnt1 on bone development based on origin and highlight its role in modulating osteoclast activity, indicating broader implications for craniofacial development and potential therapeutic avenues.

Osteocytes regulate the response of osteoclasts and osteoblasts to mechanical loading through signaling molecules, the levels of which are controlled by post-translational modification or degradation and by differential gene transcription and translation. The magnitude and mode of bone tissue deformation that elicits a transcriptional response in individual osteocytes in situ has been difficult to quantify. We measured SOST, Wnt11, TNF, and FRZB gene expression in osteocytes within loaded and unloaded control porcine trabecular bone explants using RNAScope® and compared the local tissue level strain and strain gradient—which we used as an indicator of potential poroelastic fluid flow—in the tissue surrounding osteocytes with high vs. low gene expression. The measured expression of all four genes differed between loaded and unloaded explants, on average, with the mean SOST expression level decreasing by 45%. In the loaded explants, gene expression was altered from baseline in about 30% of the osteocytes, and they were surrounded by tissue with higher strain and strain gradient than the 20 to 25% of osteocytes that remained near baseline expression. Both deviatoric strain and hydrostatic strain gradient were sensitive and specific predictors of the mechanobiological response for individual genes as well as combinations. SOST expression was highly related to elevated strain gradient, providing evidence that osteocytes respond to fluid flow in the lacunar-canalicular system.

To investigate the mechanism by which circ_EPHB4 regulates temozolomide (TMZ) sensitivity of glioma cells through the miR-424-5p/Wnt3 signal axis. We detected the expression levels of circ_EPHB4, miR-424-5p and Wnt3 mRNA in glioma specimens from 25 patients with primary glioma and 25 patients experiencing relapse following temozolomide-based chemotherapy and in TMZ-sensitive and -resistant glioma A172 and SHG44 cells with circ_EPHB4 knockdown using qRT-PCR, and Wnt3 protein expression level was detected with Western blotting. Cell viability, colony-forming ability, and apoptosis of the cells with circ_EPHB4 knockdown were assessed, and the targeted regulation relationship between circ_EPHB4, miR-424-5p, and Wnt3 was verified by dual luciferase reporter assay and RNA immunoprecipitation (RIP) experiments. The effect of circ_EPHB4 knockdown on tumorigenesis of glioma cells was evaluated in subcutaneous tumor-bearing nude mouse models. The expression of circ_EPHB4 was significantly increased in glioma tissues and cells as compared with normal neural tissues and astrocytes (P=0.014). In TMZ-resistant glioma cells, circ_EPHB4 knockdown resulted in an obvious reduction of IC50 value of TMZ, inhibited cell colony formation, and promoted cell apoptosis, and these effects were reversed by miR-424-5p knockdown. The expressions of miR-424-5p and circ_EPHB4 were negatively correlated in glioma tissues (P=0.011). MiR-424-5p knockdown also attenuated the effect of circ_EPHB4 knockdown on expressions of PCNA, P-gp, MRP1 and bax. Circ_EPHB4 regulates Wnt3 expression through "sponge adsorption" of miR-424-5p, thereby modulating TMZ-resistant glioblastoma cell clonogenesis, apoptosis, and TMZ sensitivity, suggesting the potential of circ_EPHB4 as a therapeutic target for reversing drug resistance of gliomas.