Affiliation: | 1. Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China;2. Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China;3. Regenerative Immunology and Aging, Berlin-Brandenburger Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany;4. Department of Pathology, Chinese PLA General Hospital, Beijing, China;5. Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland;6. Institute of Biophysics, Chinese Academy of Sciences, Beijing, China |
Abstract: | Prostate cancer (PCa) is one of the major health problems of the aging male. The roles of dysregulated microRNAs in PCa remain unclear. In this study, we mined the public published data and found that miR-487a-3p was significantly downregulated in 38 pairs of clinical prostate tumor tissues compared with the normal tissues. We further verified this result by in situ hybridization on tissue chip and quantitative real-time polymerase chain reaction (qRT-PCR) in PCa/normal cells. miR-487a-3p targeting of cyclin D1 (CCND1) was identified using bioinformatics, qRT-PCR and western blot analyses. The cellular proliferation, cell cycle, migration, and invasion were assessed by cell counting kit-8, flow cytometry analysis and transwell assay. We discovered that overexpression of miR-487a-3p suppressed PCa cell growth, migration, invasion by directly targeting CCND1. Knockdown of CCND1 in PCa cells showed similar results. Meanwhile, the expression level of CCND1 was significantly upregulated in the PCa tissues and cell lines, which presented negative correlation with the expression of miR-487a-3p. More important, we demonstrated significantly reduced growth of xenograft tumors of stable miR-487a-3p-overexpressed human PCa cells in nude mice. Taken together, for the first time, our results revealed that miR-487a-3p as a tumor suppressor of PCa could target CCND1. Our finding might reveal miR-487a-3p could be potentially contributed to the pathogenesis and a clinical biomarker or the new potential therapeutic target of PCa. |