4.5 Article

Long non-coding RNA ARAP1-AS1 promotes the progression of bladder cancer by regulating miR-4735-3p/NOTCH2 axis

期刊

CANCER BIOLOGY & THERAPY
卷 20, 期 4, 页码 552-561

出版社

TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2018.1538613

关键词

ARAP1-AS1; miR-4735-3p; NOTCH2; proliferation; bladder cancer

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资金

  1. National Science Foundation of China [81400701]

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Accumulative reports have documented the critical functions of long non-coding RNAs (lncRNAs) in the progression of malignant tumors, including bladder cancer (BCa). LncRNA ARAP1-AS1 was chosen to be the object of this study due to it was significantly upregulated in the BCa samples of TCGA database. qRT-PCR further validated the dysregulation of ARAP1-AS1 in 88 pairs of BCa tissues and six BCa cells. Kaplan Meier analysis was utilized to analyze the prognostic value of ARAP1-AS1 for patients with BCa. To evaluate the oncogenic property of ARAP1-AS1 in bladder cancer, loss-of-function assays were conducted in two BCa cells in which ARAP1-AS1 was expressed highest. Mechanically, ARAP1-AS1 was enriched in the cytoplasm of BCa cells, suggesting that ARAP1-AS1 might act as a ceRNA to regulate gene expression and biological processes in bladder cancer. It was certified that ARAP1-AS1 can bind with miR-4735-3p in BCa cells. Moreover, functional assays supported the hypothesis that miR-4735-3p is a tumor suppressor in BCa. Additionally, NOTCH2 mRNA could be targeted by miR-4735-3p in BCa cells. The results of all mechanism experiments indicated that ARAP1-AS1 regulated miR-4735-3p/NOTCH2 axis in BCa by acting as a ceRNA. All our research findings may bring novel insights into the treatment of bladder cancer.

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