Bladder cancer (BC) is the fourth and tenth most common malignancy in men and women worldwide, respectively. The complexity of the molecular biological mechanism behind BC is a major contributor to the lack of effective treatment management of the disease. The development and genesis of BC are influenced by mitochondrial retrograde control and mitochondria-nuclear cross-talk. However, the role of mitochondrial-related genes in BC remains unclear. In this study, we analyzed TCGA datasets and identified 752 DE-MRGs in BC samples, including 313 down-regulated MRGs and 439 up-regulated MRGs. Then, the results of machine-learning screened four critical diagnostic genes, including GLRX2, NMT1, PPP2R2B and TRAF3IP3. Moreover, we analyzed their prognostic value and confirmed that only PPP2R2B was associated with clinical prognosis of BC patients and Cox regression assays validated that PPP2R2B expression was a distinct predictor of overall survival in BC patients. Them, we performed RT-PCR and found that PPP2R2B expression was distinctly decreased in BC specimens and cell lines. Functional experiments revealed that overexpression of PPP2R2B distinctly suppressed the proliferation, migration and invasion of BC cells via Wnt signaling pathway. In summary, these research findings offer potential molecular markers for the diagnosis and prognosis of BC, with the discovery of PPP2R2B particularly holding significant biological and clinical significance. This study provides valuable clues for future in-depth investigations into the molecular mechanisms of BC, as well as the development of new diagnostic markers and therapeutic targets.

中文翻译：

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线粒体相关基因综合分析表明PPP2R2B是一种新型生物标志物并通过Wnt信号通路促进膀胱癌进展

膀胱癌（BC）分别是全球男性和女性中第四和第十大最常见的恶性肿瘤。BC 背后分子生物学机制的复杂性是导致该疾病缺乏有效治疗管理的主要原因。BC的发生和发生受到线粒体逆行控制和线粒体-核相互作用的影响。然而，线粒体相关基因在 BC 中的作用仍不清楚。在本研究中，我们分析了 TCGA 数据集，并在 BC 样本中鉴定了 752 个 DE-MRG，其中包括 313 个下调的 MRG 和 439 个上调的 MRG。然后，机器学习的结果筛选出四个关键的诊断基因，包括GLRX2、NMT1、PPP2R2B和TRAF3IP3。此外，我们分析了它们的预后价值，并证实只有 PPP2R2B 与 BC 患者的临床预后相关，Cox 回归分析验证了 PPP2R2B 表达是 BC 患者总体生存的独特预测因子。我们对他们进行了 RT-PCR，发现 BC 标本和细胞系中 PPP2R2B 的表达明显降低。功能实验表明，PPP2R2B的过表达通过Wnt信号通路明显抑制BC细胞的增殖、迁移和侵袭。总之，这些研究结果为BC的诊断和预后提供了潜在的分子标志物，其中PPP2R2B的发现尤其具有重要的生物学和临床意义。该研究为今后深入研究BC的分子机制以及开发新的诊断标志物和治疗靶点提供了宝贵的线索。