College of Clinic Medical, North China University of Science and Technology, Tangshan, China.
North China of Science and Technology Affiliated Hospital, Tangshan, China.
Biol Direct. 2024 Feb 26;19(1):17. doi: 10.1186/s13062-024-00461-6.
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.
膀胱癌（BC）分别是男性和女性中第四和第十常见的恶性肿瘤。BC 背后的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 的发展和发生受到线粒体逆行控制和线粒体-核交叉对话的影响。然而，线粒体相关基因在 BC 中的作用尚不清楚。在本研究中，我们分析了 TCGA 数据集，鉴定了 752 个 DE-MRGs 在 BC 样本中，包括 313 个下调的 MRGs 和 439 个上调的 MRGs。然后，机器学习的结果筛选出四个关键诊断基因，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 患者总生存率的显著预测因子。然后，我们进行了 RT-PCR，发现 PPP2R2B 在 BC 标本和细胞系中的表达明显降低。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，发现 PPP2R2B 具有特别重要的生物学和临床意义。这项研究为深入研究 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有价值的线索。
