miR­30c suppresses prostate cancer survival by targeting the ASF/SF2 splicing factor oncoprotein.

ABSTRACT

Our previous study revealed that microRNA (miR) ­30c represents a potential tumor suppressor gene, the expression of which is associated with decreased oncogenic potential in prostate cancer (PCa) cell lines. However, the functional role and underlying mechanisms of miR­30c in PCa remain to be fully elucidated. Reverse transcription­quantitative polymerase chain reaction and immunohistochemical analysis were used to detect the expression levels of alternative splicing factor/splicing factor 2 (ASF/SF2) in PCa tissues. A luciferase reporter assay was used to investigate whether ASF/SF2 may be a direct target gene of miR­30c. In addition, the effects of miR­30c on the proliferation and apoptosis of PCa cell lines were examined, following transfection with miR­30c mimics. Furthermore, correlation analysis was performed to investigate the relationship between the expression of miR­30c and ASF/SF2 and various clinicopathological parameters of patients with PCa. The present results demonstrated that PCa tissues exhibited higher levels of alternative splicing factor/splicing factor 2 (ASF/SF2), compared with normal tissues. In addition, miR­30c was revealed to targete the 3'­untranslated region of the ASF/SF2 gene, causing a decrease in the mRNA and protein levels of ASF/SF2. Furthermore, miR­30c was reported to decrease cell proliferation, increase the percentage of cells in the G1 cell cycle phase, and promote apoptosis through the inhibition of ASF/SF2. Following correlation analysis using patient samples, the expression of ASF/SF2 was revealed to be tightly correlated with the pathological stage of PCa and biochemical recurrence (BCR). In addition, patients with PCa exhibiting low expression levels of miR­30c and high expression of ASF/SF2 had significantly lower rates of BCR­free survival. In conclusion, the present study suggested that the tumor suppressor miR­30c may be involved in PCa tumorigenesis, possibly via targeting ASF/SF2. The combined analysis of the expression of ASF/SF2 and miR­30c may be a valuable tool for early prediction of BCR in patients with PCa following radical prostatectomy.