State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Medical Laboratory of the Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
Cancer Biol Ther. 2024 Dec 31;25(1):2386753. doi: 10.1080/15384047.2024.2386753. Epub 2024 Aug 3.
Nephroblastoma, an overexpressed gene (NOV) protein, plays an important role in proliferation, differentiation, angiogenesis, adhesion, invasion and tumorigenesis, but the function of amino-truncated NOV is different. This study is to investigate the role of amino-truncated NOV in the progression of bladder cancer. Using immunohistochemistry and Western blot analysis, we detected the amino-truncated NOV in bladder cancer, and statistical analysis was performed to estimate the association between the expression of amino-truncated NOV and the patient's prognosis by SPSS 19.0. With transduction of amino-truncated NOV, we evaluated alteration for proliferation, migration, invasion and chemoresistance in bladder cancer cells, as well as some proteins related to Wnt/β-catenin pathway and epithelial-mesenchymal transition. The truncated variant of the NOV protein was located in a nucleus other than the cytoplasm and highly expressed in bladder cancer, which was also linked to higher pathological grade and positive lymph node metastasis as well as recurrence. The exact sequence of this truncated protein was confirmed, and it was a 26-kDa splicing. The truncated NOV protein found in bladder cancer was cut at the 187th amino acid of the full-length protein. It was also involved in bladder cancer progression and chemoresistance through a mechanism involving epithelial-mesenchymal transition (EMT) and the Wnt/β-catenin signaling pathway. Our findings provide experimental evidence that the nuclear NOV protein expression is a potential biomarker in the prognostic evaluation of bladder cancer and enhanced amino-truncated NOV expression is potentially important for bladder cancer cell invasion, metastasis and chemoresistance during progression.
肾母细胞瘤过表达基因(NOV)蛋白在增殖、分化、血管生成、黏附、侵袭和肿瘤发生中起重要作用,但氨基酸截断 NOV 的功能不同。本研究旨在探讨氨基酸截断 NOV 在膀胱癌进展中的作用。采用免疫组化和 Western blot 分析检测膀胱癌中氨基酸截断 NOV 的表达,采用 SPSS 19.0 统计分析估计氨基酸截断 NOV 表达与患者预后的关系。通过转导氨基酸截断 NOV,我们评估了膀胱癌细胞增殖、迁移、侵袭和化疗耐药性的变化,以及与 Wnt/β-catenin 通路和上皮间质转化相关的一些蛋白。NOV 蛋白的截断变异位于核内而不是细胞质中,在膀胱癌中高表达,与较高的病理分级、阳性淋巴结转移和复发有关。我们确认了该截断蛋白的确切序列,它是一种 26kDa 的剪接体。在膀胱癌中发现的截断 NOV 蛋白在全长蛋白的第 187 位氨基酸处被截断。它还通过涉及上皮间质转化(EMT)和 Wnt/β-catenin 信号通路的机制参与膀胱癌的进展和化疗耐药性。我们的研究结果提供了实验证据,表明核 NOV 蛋白表达是膀胱癌预后评估的潜在生物标志物,增强的氨基酸截断 NOV 表达在膀胱癌细胞侵袭、转移和化疗耐药性的进展中可能具有重要意义。