Department of Urology, Tianjin First Central Hospital, Tianjin 300191, PR China.
Department of Pathology, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, PR China.
Gene. 2018 Dec 30;679:314-319. doi: 10.1016/j.gene.2018.09.022. Epub 2018 Sep 12.
Bladder cancer (BC) has been regarded as the most common malignancy of the urinary system worldwide. With lack of investigations for molecular pathogenesis underlying that develop BC, the therapeutic efficacy of several therapeutic approaches existing is still unsatisfactory. Here, our study aimed to explore the potentially biological function of MAN1B1 on BC. In this study, MAN1B1 expression level in BC tissues and normal tissues was analyzed based on The Cancer Genome Atlas (TCGA) data and correlation between its expression and prognosis was determined using Kaplan-Meier analysis. Knockout of MAN1B1 was performed using silencing RNA and the efficacy of MAN1B1 knockout was identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. The BC cells proliferation was assessed by Cell Counting Kit-8 (CCK8) assay, and then the cells apoptosis was detected by Annexin V-fluorescein isothiocyanate (Annexin V-FITC)/propidium iodide (PI) staining and flow cytometry following MAN1B1 knocked down by small interfering RNA. Protein kinase B (AKT) signaling was evaluated by detecting related markers, namely AKT, p-AKT, 4E-BP-1 and Bax using western blot assay. As a result, the MAN1B1 expression was higher in BC tissues than those in normal tissues, besides, its overexpression was associated with poor prognosis. Moreover, MAN1B1 reduction by silencing RNA approach resulted in BC cells proliferation suppression and BC cells apoptosis promotion. Finally, AKT signaling activity was inhibited by MAN1B1 silencing. Taken together, these results unraveled that MAN1B1 may act on an oncogenic action in BC, which improved the likelihood of MAN1B1 taking on a promising prognostic biomarker and a potential target for treating BC.
膀胱癌(BC)已被认为是全球最常见的泌尿系统恶性肿瘤。由于缺乏对导致 BC 发生的分子发病机制的研究,几种现有治疗方法的治疗效果仍不理想。在这里,我们的研究旨在探索 MAN1B1 在 BC 中的潜在生物学功能。在这项研究中,基于癌症基因组图谱(TCGA)数据分析了 BC 组织和正常组织中 MAN1B1 的表达水平,并通过 Kaplan-Meier 分析确定了其表达与预后的相关性。使用沉默 RNA 敲除 MAN1B1,并通过定量逆转录聚合酶链反应(qRT-PCR)分析鉴定 MAN1B1 敲除的效果。通过细胞计数试剂盒-8(CCK8)测定评估 BC 细胞增殖,然后通过 Annexin V-荧光素异硫氰酸酯(Annexin V-FITC)/碘化丙啶(PI)染色和流式细胞术检测 MAN1B1 敲低后 BC 细胞凋亡。通过 Western blot 测定评估蛋白激酶 B(AKT)信号,即用 AKT、p-AKT、4E-BP-1 和 Bax 等相关标记物评估。结果表明,BC 组织中 MAN1B1 的表达高于正常组织,此外,其过表达与预后不良有关。此外,沉默 RNA 方法降低 MAN1B1 的表达导致 BC 细胞增殖抑制和 BC 细胞凋亡促进。最后,MAN1B1 沉默抑制了 AKT 信号活性。总之,这些结果表明,MAN1B1 可能在 BC 中发挥致癌作用,这增加了 MAN1B1 作为有前途的预后生物标志物和治疗 BC 的潜在靶点的可能性。