Bladder cancer is the most frequent malignancy of the urinary tract and the seventh most common cancer worldwide. The abnormal expression of microRNAs has been frequently observed in various types of human cancers, including bladder cancer. In addition, an increasing body of evidence has demonstrated that microRNAs are potential targets for cancer diagnosis, treatments and prognosis. The aim of the present study was to investigate the expression patterns and potential roles of microRNA‑539 (miR‑539) in bladder cancer and its underlying mechanism. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect miR‑539 expression in the bladder cancer tissues and cell lines. Following transfection, MTT and cell invasion assays were used to investigate the effects of miR‑539 overexpression or IGF1R underexpression on bladder cancer cell proliferation and invasion. Bioinformatics analysis, a luciferase reporter assay, RT‑qPCR and western blot analysis were utilized to determine the potential targets of miR‑539 in bladder cancer. The results revealed that miR‑539 levels were relatively decreased in bladder cancer tissues and cell lines when compared with those observed in the matched adjacent normal bladder tissues and normal bladder epithelial cell line. miR‑539 expression was associated with the tumor stage and lymph node metastasis of patients with bladder cancer. In addition, the expression of miR‑539 suppressed bladder cancer cell proliferation and invasion. Insulin like growth factor 1 receptor (IGF‑1R) was identified as a direct target of miR‑539, and miR‑539 was also observed to regulate the protein kinase B and extracellular signal‑regulated kinases signaling pathways. IGF‑1R was markedly upregulated in bladder cancer tissues and negatively associated with miR‑539 expression levels. Furthermore, IGF‑1R knockdown in bladder cancer cells significantly inhibited cell proliferation and invasion. To the best of our knowledge, these results demonstrated for the first time that miR‑539 may act as a tumor suppressor and serve important roles in tumorigenesis and progression of bladder cancer. Thus, miR‑539/IGF‑1R may be a potential therapeutic target for the treatment of bladder cancer.
Molecular medicine reports. 2018 Jan 25 [Epub ahead of print]
Guiyi Liao, Fangmin Chen, Jinbiao Zhong, Xinan Jiang
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China., Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.