Xie Yu, Zhu Shuai, Zang Jinglei, Wu Guanlin, Wen Yuheng, Liang Yu, Long Ying, Guo Weiming, Zang Chuanbing, Hu Xiang, Fan Gang, Xiang Shuanglin, Zhang Jian
Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, Hunan Normal University, 410081 Changsha, China.
Department of Urology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, 410013 Changsha, China.
J Cancer. 2021 Jun 22;12(17):5114-5124. doi: 10.7150/jca.58049. eCollection 2021.
Activity-dependent neuroprotective protein (ADNP) is vital for embryonic development and brain formation. Besides, the upregulated expression of ADNP enhances tumorigenesis in some human tumors like bladder cancer (BC). However, the potential roles of ADNP in drug resistance and the related mechanisms in BC is unknown. We performed this study to elucidate the influence of ADNP in the chemoresistance of BC and tried to explore the underlying molecular mechanism. The expressions of ADNP in BC from progression and non-progression patient specimens were measured by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). experiments including colony formation, cell counting kit-8 (CCK-8), wound healing, and tumorigenesis assay were performed to explore the effects of ADNP on chemoresistance of BC. The impacts of ADNP on TGF-β/Smad signaling pathways were explored by western blot. Our results showed that the expression of ADNP mRNA and protein were significantly upregulated in BC tissues of the patients who suffered tumor-progression via RT-PCR and western blot. Cox regression survival analysis revealed that patients with high ADNP expression closely linked to shorter tumor-free survival. ADNP downregulation in BC showed more sensitive to cisplatin , while ADNP overexpression showed the opposite results. Additionally, we confirmed that ADNP promoted cell migration and EMT, thereby inducing cisplatin resistance, which may be related to TGF-β / Smad signaling pathway.
活性依赖的神经保护蛋白（ADNP）对胚胎发育和脑形成至关重要。此外，ADNP表达上调会增强某些人类肿瘤（如膀胱癌，BC）的肿瘤发生。然而，ADNP在膀胱癌耐药性中的潜在作用及相关机制尚不清楚。我们进行本研究以阐明ADNP对膀胱癌化疗耐药性的影响，并试图探索其潜在分子机制。通过定量实时PCR（qRT-PCR）和免疫组化（IHC）检测进展期和非进展期患者膀胱癌标本中ADNP的表达。进行了包括集落形成、细胞计数试剂盒-8（CCK-8）、伤口愈合和肿瘤发生试验等实验，以探索ADNP对膀胱癌化疗耐药性的影响。通过蛋白质印迹法探究ADNP对转化生长因子-β/ Smad信号通路的影响。我们的结果显示，通过RT-PCR和蛋白质印迹法发现，在肿瘤进展的患者的膀胱癌组织中，ADNP mRNA和蛋白的表达显著上调。Cox回归生存分析显示，ADNP高表达患者与无瘤生存期缩短密切相关。膀胱癌中ADNP下调对顺铂更敏感，而ADNP过表达则显示相反结果。此外，我们证实ADNP促进细胞迁移和上皮-间质转化，从而诱导顺铂耐药，这可能与转化生长因子-β/ Smad信号通路有关。
