Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou, China.
J Cell Biochem. 2019 Apr;120(4):6596-6604. doi: 10.1002/jcb.27954. Epub 2018 Nov 13.
In recent years, the NOTCH signaling pathway has been gradually studied in human malignancies. Inactivation of the NOTCH signaling pathway was uncovered to be correlated with the carcinogenesis of bladder cancer (BCa). Nevertheless, the specific molecular mechanism of NOTCH1 (one of the core factors of the NOTCH signaling pathway) is not well elucidated in BCa. This study focused on the mechanism by which NOTCH1 affects the biological behaviors of BCa cells. According to the experimental results of quantitative real-time polymerase chain reaction, NOTCH1 was dysregulated in BCa tissues and cell lines. The prognostic value of NOTCH1 for the patients with BCa was determined using the Kaplan-Meier method. Mechanism investigations revealed that NOTCH1 is a target of miR-34c-5p in BCa. Furthermore, microarray analysis was used to find the dysregulated long noncoding RNAs (lncRNA), which can bind with miR-34c-5p. Mechanism experiments further demonstrated the rationality of the HCG18-miR-34c-5p-NOTCH1 pathway. Functional assays were then applied to validate the inhibitory influences of NOTCH1 on the proliferation and migration of BCa cells. Furthermore, the inhibitory effects of NOTCH1 could be affected by miR-34c-5p or lncRNA HCG18. All findings in this study revealed that NOTCH1 suppresses the BCa progression by cooperating with lncRNA HCG18 and miR-34c-5p.
近年来，NOTCH 信号通路在人类恶性肿瘤中的研究逐渐增多。研究发现 NOTCH 信号通路失活与膀胱癌（BCa）的发生有关。然而，NOTCH1（NOTCH 信号通路的核心因子之一）在 BCa 中的具体分子机制尚不清楚。本研究重点探讨了 NOTCH1 影响 BCa 细胞生物学行为的机制。根据定量实时聚合酶链反应的实验结果，NOTCH1 在 BCa 组织和细胞系中失调。Kaplan-Meier 法确定了 NOTCH1 对 BCa 患者的预后价值。机制研究表明，NOTCH1 是 BCa 中 miR-34c-5p 的靶基因。此外，还使用微阵列分析找到了与 miR-34c-5p 结合的失调长非编码 RNA（lncRNA）。进一步的机制实验证明了 HCG18-miR-34c-5p-NOTCH1 通路的合理性。然后进行功能测定以验证 NOTCH1 对 BCa 细胞增殖和迁移的抑制作用。此外，miR-34c-5p 或 lncRNA HCG18 可影响 NOTCH1 的抑制作用。本研究的所有发现表明，NOTCH1 通过与 lncRNA HCG18 和 miR-34c-5p 合作抑制 BCa 的进展。
