NOTCH1 regulates the proliferation and migration of bladder cancer cells by cooperating with long non‐coding RNA HCG18 and microRNA‐34c‐5p

• Published in: Journal of cellular biochemistry Vol. 120; no. 4; pp. 6596 - 6604
• Main Authors: Xu, Zhihui, Huang, Banggao, Zhang, Qi, He, Xiang, Wei, Haibin, Zhang, Dahong
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2019
• Subjects: Bladder; Bladder cancer; bladder cancer (BCa); Cancer; Carcinogenesis; Carcinogens; Cell migration; Cell proliferation; Deactivation; HCG18; Inactivation; miRNA; miR‐34c‐5p; NOTCH1; Notch1 protein; Polymerase chain reaction; proliferation; Ribonucleic acid; RNA; Signal transduction; Signaling; NOTCH1; proliferation; bladder cancer (BCa); miR-34c-5p; HCG18
• ISSN: 0730-2312; 1097-4644; 1097-4644
• DOI: 10.1002/jcb.27954

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. NOTCH1 is a poor prognostic factor for patients with bladder cancer (BCa). NOTCH1 acts as an oncogene to promote BCa progression. NOTCH1 can participate in a competing endogenous RNA (ceRNA) model by cooperating with lncRNA HCG18 and miR‐34c‐5p.