Sakai Andresa Hiromi, Pereira Érica Romão, Santos Anna Gabriele Prado Dos, Quadreli Débora Hipólito, Lima Luan Vitor Alves de, Ribeiro Diego Luis, Rahimirad Samira, Mathias Carolina, Nóbrega Monyse de, Mantovani Mário Sérgio, Scantamburlo Alves Fernandes Glaura, Cólus Ilce Mara de Syllos, Serpeloni Juliana Mara
Post-Graduation Program in Genetics and Molecular Biology, Department of General Biology, State University of Londrina, Londrina 86057-970, Brazil.
Post-Graduation Program in Experimental Pathology, Department of Immunology, Parasitology and General Pathology, State University of Londrina, Londrina 86057-970, Brazil.
Pharmaceuticals (Basel). 2025 Sep 16;18(9):1382. doi: 10.3390/ph18091382.
: Urothelial bladder carcinoma (UBC) is one of the most prevalent malignancies worldwide, and efforts have intensified to identify molecular markers that improve the prognosis and reduce treatment costs. Among the regulators of tumor behavior, microRNAs (miRNAs) have emerged as promising biomarkers for cancer diagnoses and treatment. The modulation of miR-25-3p has been associated with pancreatic, colorectal, and lung cancers; its role in UBC remains poorly explored. In this study, we investigated the effects of miR-25-3p modulation in a high-grade and muscle-invasive bladder cancer (MIBC) cell line (T24), using in vitro functional assays and bioinformatics approaches. Bioinformatics analyses using TCGA-BLCA datasets revealed that miR-25-3p is upregulated in tumor tissues compared to non-tumor tissues, prompting an investigation into its molecular targets and related pathways. The transfection of T24 cells with an miR-25-3p mimic and inhibitor led to respective overexpression (11.16-fold) and downregulation (-2.82-fold) compared to the negative control. Functionally, miR-25-3p overexpression increased cell proliferation, viability, and migration, while its inhibition decreased the cell migration capacity. A gene expression analysis revealed that miR-25-3p overexpression resulted in the downregulation of , , , , , , and , whereas , , and were upregulated, suggesting a role in both migration and ferroptosis regulation. In the inhibitor group, increased and decreased expression further supported this connection. Our results using an in vitro model for MIBC with the transfection of T24 cells suggest that miR-25-3p influences key pathways involved in oxidative stress and cell death, promoting a more aggressive tumor phenotype. The modulation of miR-25-3p impacts the behavior of T24 bladder cancer cells and may indicate its role in disease progression. Our results underscore the potential of miR-25-3p as a prognostic biomarker and support further studies considering its therapeutic relevance in managing high-grade and muscle-invasive bladder cancer.
尿路上皮膀胱癌（UBC）是全球最常见的恶性肿瘤之一，人们一直在加大力度寻找能够改善预后并降低治疗成本的分子标志物。在肿瘤行为调节因子中，微小RNA（miRNA）已成为癌症诊断和治疗中颇具前景的生物标志物。miR-25-3p的调节与胰腺癌、结直肠癌和肺癌有关；其在UBC中的作用仍有待深入研究。在本研究中，我们使用体外功能测定和生物信息学方法，研究了miR-25-3p调节在高级别肌层浸润性膀胱癌（MIBC）细胞系（T24）中的作用。使用TCGA-BLCA数据集进行的生物信息学分析显示，与非肿瘤组织相比，miR-25-3p在肿瘤组织中上调，这促使我们对其分子靶点和相关途径进行研究。与阴性对照相比，用miR-25-3p模拟物和抑制剂转染T24细胞分别导致其过表达（11.16倍）和下调（-2.82倍）。在功能上，miR-25-3p过表达增加了细胞增殖、活力和迁移能力，而其抑制则降低了细胞迁移能力。基因表达分析显示，miR-25-3p过表达导致 、 、 、 、 、 和 下调，而 、 和 上调，表明其在迁移和铁死亡调节中均起作用。在抑制剂组中， 表达增加和 表达降低进一步支持了这种联系。我们使用转染T24细胞的MIBC体外模型的结果表明，miR-25-3p影响参与氧化应激和细胞死亡的关键途径，促进更具侵袭性的肿瘤表型。miR-25-3p的调节影响T24膀胱癌细胞的行为，并可能表明其在疾病进展中的作用。我们的结果强调了miR-25-3p作为预后生物标志物的潜力，并支持进一步研究其在管理高级别肌层浸润性膀胱癌中的治疗相关性。
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