Zhu Shuai, Xu Zhenzhou, Zeng Yong, Long Ying, Fan Gang, Ding Qi, Wen Yuheng, Cao Jian, Dai Tao, Han Weiqing, Xie Yu
Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, China.
Clinical Translational Research Center, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, China.
Front Oncol. 2020 Nov 9;10:491129. doi: 10.3389/fonc.2020.491129. eCollection 2020.
Activity-dependent neuroprotective protein (ADNP), which is involved in embryonic development and neurogenesis, has been proven to be upregulated in some human tumors. However, its role in bladder cancer (BC) has never been studied.
We aimed to investigate the mechanisms by which ADNP promotes the progression of BC.
ADNP expressions in BC cell lines and paired BC and adjacent normal tissues were measured by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. Colony formation, Cell Counting Kit-8 (CCK-8), trypan blue exclusion assay, flow cytometry, and nude mice tumorigenesis assay were performed to explore the effects of ADNP on growth of BC and . The impacts of ADNP on AKT signaling pathways were measured by Western blot.
The expression of ADNP mRNA and protein was significantly upregulated in BC tissues compared with adjacent normal tissues. Immunohistochemical analysis of 221 BC and 51 adjacent normal tissue paraffin sections indicated that ADNP expression was significantly associated with histological classification and pathological T and N stages. Survival analysis revealed that patients with high ADNP expression have worse prognosis with respect to overall survival and progression-free disease. ADNP knockdown markedly delayed propagation of BC and the development of BC ADNP overexpression showed the opposite effect. In addition, ADNP can markedly promote G1-S cell cycle transition in BC cells. On the molecular level, we confirmed that ADNP mediated acceleration of G1-S transition was associated with activation of the AKT pathways in BC.
ADNP is overexpressed in BC and promotes BC growth partly through AKT pathways. ADNP is crucial in predicting the outcome of BC patients and may be a potential therapeutic target in BC.
活性依赖的神经保护蛋白（ADNP）参与胚胎发育和神经发生，已被证实在某些人类肿瘤中上调。然而，其在膀胱癌（BC）中的作用尚未得到研究。
我们旨在研究ADNP促进BC进展的机制。
通过定量实时PCR（qRT-PCR）、蛋白质印迹法和免疫组织化学检测BC细胞系以及配对的BC组织和相邻正常组织中ADNP的表达。进行集落形成实验、细胞计数试剂盒-8（CCK-8）实验、台盼蓝排斥实验、流式细胞术和裸鼠成瘤实验，以探讨ADNP对BC生长的影响。通过蛋白质印迹法检测ADNP对AKT信号通路的影响。
与相邻正常组织相比，BC组织中ADNP mRNA和蛋白质的表达显著上调。对221例BC组织和51例相邻正常组织石蜡切片进行免疫组织化学分析表明，ADNP表达与组织学分类以及病理T和N分期显著相关。生存分析显示，ADNP高表达的患者在总生存期和无进展生存期方面预后较差。敲低ADNP可显著延迟BC的增殖以及BC的发展，过表达ADNP则显示出相反的效果。此外，ADNP可显著促进BC细胞从G1期向S期的细胞周期转变。在分子水平上，我们证实ADNP介导的G1-S转变加速与BC中AKT通路的激活有关。
ADNP在BC中过表达，并部分通过AKT通路促进BC生长。ADNP对于预测BC患者的预后至关重要，可能是BC潜在的治疗靶点。
