miRNA-30a functions as a tumor suppressor by downregulating cyclin E2 expression in castration-resistant prostate cancer.

MicroRNAs (miRNAs) act as tumor promoters or tumor suppressors in different human malignancies. In the current study, using an Agilent miRNA microarray, miR-30a was found to be a significantly downregulated miRNA in castration-resistant prostate cancer (CRPC) tissues, compared with androgen-dependent prostate cancer tissues. Aberrant expression of cyclin E2 (CCNE2) has been reported in a variety of types of cancer including prostate cancer, and correlates with clinical outcome. The purpose of the current study was to determine the functions of miR-30a in CRPC cell lines and identify whether CCNE2 was regulated by miR-30a. To analyze the associations between miR-30a and CCNE2 expression levels, pathological specimens were collected, and reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining were conducted. The effect of miR-30a overexpression on CRPC cell lines and the predicted target gene, CCNE2, were evaluated by MTT assay, flow cytometry, tumor formation, luciferase reporter assay and western blotting. miR-30a overexpression resulted in a significant suppression of cell growth in vitro, and reduced tumorigenicity in vivo. miR-30a repressed the expression of CCNE2 through binding to its 3-untranslated region. CCNE2 was observed to be overexpressed in patients with CRCP and had an approximately inverse correlation with the level of miR-30a. The results suggest that miR-30a may function as a novel tumor suppressor in CRPC. Its anti-oncogenic activity may occur by the reduced expression of a distinct cell cycle protein, CCNE2.