Cdc42, a member of the Rho GTPases family, is involved in the regulation of several cellular functions including cell cycle progression, survival, transcription, actin cytoskeleton organization and membrane trafficking. Diabetes is a chronic and metabolic disease, characterized as glycometabolism disorder induced by insulin deficiency related to β cell dysfunction and peripheral insulin resistance (IR). Diabetes could cause many complications including diabetic nephropathy (DN), diabetic retinopathy and diabetic foot. Furthermore, hyperglycemia can promote tumor progression and increase the risk of malignant cancers. In this review, we summarized the regulation of Cdc42 in insulin secretion and diabetes-associated diseases. Organized researches indicate that Cdc42 is a crucial member during the progression of diabetes, and Cdc42 not only participates in the process of insulin synthesis but also regulates the insulin granule mobilization and cell membrane exocytosis via activating a series of downstream factors. Besides, several studies have demonstrated Cdc42 as participating in the pathogenesis of IR and DN and even contributing to promote cancer cell proliferation, survival, invasion, migration, and metastasis under hyperglycemia. Through the current review, we hope to cast light on the mechanism of Cdc42 in diabetes and associated diseases and provide new ideas for clinical diagnosis, treatment, and prevention.

Despite great improvements in the diagnosis and treatment of neoplasms, metastatic disease is still the leading cause of death in cancer patients, with mortality rates still rising. Given this background, new ways to treat cancer will be important for development of improved cancer control strategies. Cdc42 is a member of the Rho GTPase family and plays an important role in cell-to-cell adhesion, formation of cytoskeletal structures, and cell cycle regulation. It thus influences cellular proliferation, transformation, and homeostasis, as well as the cellular migration and invasion processes underlying tumor formation. Cdc42 acts as a collection point for signal transduction and regulates multiple signaling pathways. Moreover, recent studies show that in most human cancers Cdc42 is abnormally expressed and promoting neoplastic growth and metastasis. Regarding possible new treatments for cancer, miRNA and small molecules targeting Cdc42 and related pathways have been recently found to be effective on cancer. In this review, we analyze the newly recognized regulation mechanisms for Cdc42 and Cdc42-related signal pathways, and particularly new treatments using small molecules and miRNAs to inhibit the abnormal overexpression of Cdc42 that may slow down the metastasis process, improve cancer therapy and lead to novel strategies for development of antineoplastic drugs.

Background. Diabetes is a progressive metabolic disease characterized by hyperglycemia. Functional impairment of islet β cells can occur to varying degrees. This impairment can initially be compensated for by proliferation and metabolic changes of β cells. Cell division control protein 42 (Cdc42) and the microRNA (miRNA) miR-29 have important roles in β-cell proliferation and glucose-stimulated insulin secretion (GSIS), which we further explored using the mouse insulinoma cell line MIN6. Methods. Upregulation and downregulation of miR-29a and Cdc42 were accomplished using transient transfection. miR-29a and Cdc42 expression was detected by real-time PCR and western blotting. MIN6 proliferation was detected using a cell counting kit assay. GSIS under high-glucose (20.0 mM) or basal-glucose (5.0 mM) stimulation was detected by enzyme-linked immunosorbent assay. The miR-29a binding site in the Cdc42 mRNA 3′-untranslated region (UTR) was determined using bioinformatics and luciferase reporter assays. Results. miR-29a overexpression inhibited proliferation (P<0.01) and GSIS under high-glucose stimulation (P<0.01). Cdc42 overexpression promoted proliferation (P<0.05) and GSIS under high-glucose stimulation (P<0.05). miR-29a overexpression decreased Cdc42 expression (P<0.01), whereas miR-29a downregulation increased Cdc42 expression (P<0.01). The results showed that the Cdc42 mRNA 3′-UTR is a direct target of miR-29a in vitro. Additionally, Cdc42 reversed miR-29a-mediated inhibition of proliferation and GSIS (P<0.01). Furthermore, miR-29a inhibited β-catenin expression (P<0.01), whereas Cdc42 promoted β-catenin expression (P<0.01). Conclusion. By negatively regulating Cdc42 and the downstream molecule β-catenin, miR-29a inhibits MIN6 proliferation and insulin secretion.

Objective: Detrusor overactivity (DO) is a severe urological disorder in spinal cord injury (SCI) patients. Conventional pharmacological interventions, such as antimuscarinic agents, show limited therapeutic efficacy and are often associated with adverse effects. Emerging evidence indicates that prostaglandin E2 (PGE2) and its E-prostanoid 3 (EP3) receptor play a pivotal regulatory role in bladder function. This study aimed to investigate whether EP3 receptor antagonism can alleviate DO after SCI. Methods: Bladder PGE2 and cyclooxygenase-2 levels were assessed after SCI. Urodynamic alterations were evaluated by cystometry. The EP3 receptor antagonist L- 826266 (0.1 or 1.0 mg/kg) was intravenously administered to SCI rats. Urodynamic parameters, bladder cyclic adenosine monophosphate levels, histopathological changes, and preliminary systemic safety parameters were further assessed. L-826266 was also tested in PGE2-induced and acetic acid-induced overactive bladder (OAB) models and in healthy rats. Results: SCI increased bladder PGE2 and cyclooxygenase-2 levels and induced nonvoiding contractions (NVCs) during bladder storage phase. Both doses of L-826266 (0.1 and 1.0 mg/kg) increased the intercontraction interval, bladder capacity, and voiding efficiency and reduced NVC frequency in SCI rats. L-826266 also increased bladder cyclic adenosine monophosphate levels without obvious systemic toxicity or histopathological aggravation. In PGE2-induced OAB rats, L-826266 increased bladder capacity and reduced NVC frequency, whereas it had minimal effects on acetic acidinduced OAB. In healthy rats, only 1.0 mg/kg L-826266 prolonged the intercontraction interval and increased bladder capacity. Conclusion: EP3 receptor antagonist significantly reduced DO in SCI rats, which provides novel insights into the therapeutic agents for bladder dysfunction after SCI. Cite this article as: Lv LC, Xu XJ, Guo DY, et al. Therapeutic effects of prostaglandin E2 receptor subtype 3 blockade on spinal cord injury-induced detrusor overactivity. Urol Res Pract. 2026;52, doi:10.5152/tud.2026.26041