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Cell Physiol Biochem. 2018;48(2):815-826. doi: 10.1159/000491911. Epub 2018 Jul 20.

MicroRNA-374a Inhibits Aggressive Tumor Biological Behavior in Bladder Carcinoma by Suppressing Wnt/β-Catenin Signaling.

Author information

1
Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, China.
2
Center for Reproductive Medicine and Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, China.
3
Department of Thoracic Oncosurgery, Jilin Province Cancer Hospital, Changchun, China.
4
Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, China.

Abstract

BACKGROUND/AIMS:

microRNA (miR)-374a plays a crucial role in cancer progression by promoting the metastasis and proliferation of various types of malignant tumors. Because its role in bladder cancer is unknown, we investigated whether miR-374a affects the progression of bladder cancer and studied the underlying mechanism.

METHODS:

The Cancer Genome Atlas was used to analyze the clinical relevance of miR-374a. Quantitative PCR, western blotting, and luciferase and immunofluorescence assays were used to detect the expression patterns, downstream targets, and function of miR-374a in bladder cancer cells. Apoptosis was evaluated by flow cytometry after cisplatin treatment.

RESULTS:

Via in silico analysis, low levels of miR-374a were associated with poor prognosis in bladder cancer patients with distant metastasis. WNT5A was a direct target of miR-374a in two bladder cancer cell lines. miR-374a mimic abrogated the metastatic potential and invasiveness of bladder cancer cells via WNT5A downregulation in both T24 and TCCSUP human bladder cancer cells; the opposite was observed with miR-374a inhibitor. In addition, miR-374a treatment reduced the phosphorylation and nuclear translocation of β-catenin. Cisplatin treatment significantly increased the apoptosis rate. Expression levels of cancer stemness-related proteins were reduced in miR-374a mimic-pretreated cells.

CONCLUSION:

Lower expression of miR-374a is associated with poor prognosis and miR-374a improves tumor biological behavior in bladder cancer cells, suggesting that miR-374a might be a novel small-molecule therapeutic target.

KEYWORDS:

Bladder cancer; Metastasis; Mir-374a; WNT5A; Wnt/β-catenin

PMID:
30032142
DOI:
10.1159/000491911
[Indexed for MEDLINE]
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