Bladder cancer (BC) is the second most common genitourinary malignancy. Long noncoding RNA (lncRNA) is implicated in BC progression. This study delved into the underlying mechanism of lncRNA MEG3 in BC. Bioinformatics analysis predicted the expression of lncRNA MEG3, its association with the survival of BC patients, its subcellular localization, and its binding sites with miR-21-5p. Differentially expressed genes (DEGs) in the GSE13507 chip were analyzed using GEOexplorer, downstream targets of miR-21-5p were predicted from databases, and the overlapping genes were analyzed by the website Venny2.1 (https://bioinfogp.cnb.csic.es/tools/venny/index.html); their impacts on patient survival were analyzed by the Starbase database. The expression of SPRY2 and TGFBI associated with patient survival was analyzed in TCGA. RT-qPCR and western blot were performed to detect levels of MEG3, miR-21-5p, and SPRY2 in BC/SV-HUC-1 cells. Malignant biological behaviors of BC cells were detected using CCK8, flow cytometry, and Transwell assays. RNA pull-down and dual-luciferase assays were employed to verify the binding relationship of miR-21-5p with MEG3 and SPRY2. MEG3 was found to be lowly expressed in BC cells and mainly distributed in the cytoplasm. Over-expression of MEG3 was found to inhibit BC cell activity, promote apoptosis, and reduce invasion and migration. miR-21-5p was found to be highly expressed in BC cells, and its down-regulation was found to inhibit the malignant behavior of BC cells. Over-expression of miR-21-5p was found to reverse the effect of pcDNA3.1-MEG3 on BC cells. MEG3 was found to competitively bind to miR-21-5p as a ceRNA to promote SPRY2 levels. LncRNA MEG3 promotes SPRY2 expression by competitively binding to miR-21-5p, thereby inhibiting proliferation and promoting apoptosis of BC cells.

中文翻译：

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lncRNA MEG3/miR-21-5p/SPRY2在膀胱癌细胞增殖和凋亡中的作用机制

膀胱癌（BC）是第二常见的泌尿生殖系统恶性肿瘤。长非编码 RNA (lncRNA) 与 BC 进展有关。本研究深入探讨了 BC 中 lncRNA MEG3 的潜在机制。生物信息学分析预测了 lncRNA MEG3 的表达、其与 BC 患者生存的关系、其亚细胞定位及其与 miR-21-5p 的结合位点。使用GEOexplorer分析GSE13507芯片中的差异表达基因（DEG），从数据库预测miR-21-5p的下游靶标，并通过网站Venny2.1（https://bioinfogp.cnb.csic）分析重叠基因.es/tools/venny/index.html); Starbase 数据库分析了它们对患者生存的影响。在 TCGA 中分析与患者生存相关的 SPRY2 和 TGFBI 的表达。采用RT-qPCR和蛋白质印迹法检测BC/SV-HUC-1细胞中MEG3、miR-21-5p和SPRY2的水平。使用 CCK8、流式细胞术和 Transwell 检测检测 BC 细胞的恶性生物学行为。采用RNA Pull-down和双荧光素酶测定来验证miR-21-5p与MEG3和SPRY2的结合关系。MEG3在BC细胞中低表达，主要分布在细胞质中。MEG3 的过度表达被发现可以抑制 BC 细胞活性、促进细胞凋亡、减少侵袭和迁移。研究发现miR-21-5p在BC细胞中高表达，其下调可抑制BC细胞的恶性行为。发现 miR-21-5p 的过度表达可逆转 pcDNA3.1-MEG3 对 BC 细胞的影响。研究发现 MEG3 作为 ceRNA 竞争性结合 miR-21-5p，以促进 SPRY2 水平。LncRNA MEG3通过竞争性结合miR-21-5p促进SPRY2表达，从而抑制BC细胞增殖并促进凋亡。