Ke Shuai, Guo Jiayu, Wang Qinghua, Shao Haoren, He Mu, Li Tao, Qiu Tao, Guo Jia
Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
The Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Cancers (Basel). 2023 May 18;15(10):2816. doi: 10.3390/cancers15102816.
Clear cell renal cell carcinoma (ccRCC, or KIRC) is the most common type of kidney cancer, originating within the renal cortex. The current outcomes for early diagnosis and late treatment of ccRCC are unsatisfactory. Therefore, it is important to explore tumor biomarkers and therapeutic opportunities for ccRCC. In this study, we used bioinformatics methods to systematically evaluate the expression and prognostic value of Netrin family genes in ccRCC. Through our analysis, three potential biomarkers for ccRCC were identified, namely NTNG1, NTNG2, and NTN4. Moreover, we performed in vitro and in vivo experiments to explore the possible biological roles of NTN4 and found that NTN4 could regulate ccRCC development through Wnt/β-catenin signaling. We elucidate the molecular mechanism by which NTN4 modulates β-catenin expression and nuclear translocation to inhibit ccRCC progression, providing a new theoretical basis for developing therapeutic targets for ccRCC. Thus, we suggest that Netrin-related studies may offer new directions for the diagnosis, treatment, and prognosis of ccRCC patients.
透明细胞肾细胞癌（ccRCC，或KIRC）是最常见的肾癌类型，起源于肾皮质。目前ccRCC早期诊断和晚期治疗的效果并不理想。因此，探索ccRCC的肿瘤生物标志物和治疗机会具有重要意义。在本研究中，我们使用生物信息学方法系统评估了Netrin家族基因在ccRCC中的表达及预后价值。通过分析，我们鉴定出了三种ccRCC潜在生物标志物，即NTNG1、NTNG2和NTN4。此外，我们进行了体外和体内实验以探索NTN4可能的生物学作用，发现NTN4可通过Wnt/β-连环蛋白信号通路调节ccRCC的发展。我们阐明了NTN4调节β-连环蛋白表达和核转位以抑制ccRCC进展的分子机制，为开发ccRCC治疗靶点提供了新的理论依据。因此，我们认为Netrin相关研究可能为ccRCC患者的诊断、治疗和预后提供新方向。
