Abstract
Recently miR-182 has been reported to be over-expressed in prostate cancer (PC) tissues, however detailed functional analysis of miR-182-5p has not been carried out. The purpose of this study was to: 1. analyze the function of miR-182-5p in prostate cancer, 2. assess its usefulness as a tumor marker, 3. identify miR-182-5p target genes in PC, 4. investigate the potential for miR-182-5p inhibitor to be used in PC treatment. Initially we found that miR-182-5p expression was significantly higher in prostate cancer tissues and cell lines compared to normal prostate tissues and cells. Moreover high miR-182-5p expression was associated with shorter overall survival in PC patients. To study the functional significance of miR-182-5p, we knocked down miR-182-5p with miR-182-5p inhibitor. After miR-182-5p knock-down, prostate cancer cell proliferation, migration and invasion were decreased. We identified FOXF2, RECK and MTSS1 as potential target genes of miR-182-5p using several algorithms which was confirmed by 3’UTR luciferase assay and Western analysis. Knock-down of miR-182-5p also significantly decreased in vivo prostate tumor growth. In conclusion this is the first report documenting that over-expression of miR-182-5p is associated with prostate cancer progression and potentially useful as a prognostic biomarker. Also knock down of miR-182-5p in order to increase expression of tumor suppressor genes FOXF2, RECK and MTSS1 may be of therapeutic benefit in prostate cancer treatment.
Highlights
Prostate cancer (PC) is one of the most common malignancies in U.S males [1]
Several microRNAs have been identified as oncogenic in prostate cancer based on their increased expression in prostate cancer tissues or prostate cancer cell lines [10,11,12,13,14]
One report has shown that miR-182 is a tumor suppressor in a lung cancer cell line [17], while miR-182-5p has been reported to be an oncogene in several cancers [18,19,20,21,22,23]
Summary
Prostate cancer (PC) is one of the most common malignancies in U.S males [1]. The etiology of PC is largely unknown, several risk factors such as ethnicity, family history, and age are associated with the disease [2]. A number of miRNAs have been identified and reported to be important in several cancers [6]. MiRNAs bind to the 3’ untranslated region (UTR) of target mRNA and represses translation from mRNA to protein or induce mRNA cleavage, thereby regulating the expression of target genes such as tumor suppressor or oncogenes [8,9]. MiR-182 has been reported to be over-expressed in prostate cancer [10]. We hypothesize that miR-182-5p may function as an oncogene and be a new molecular biomarker in prostate cancer. To test this hypothesis, we initially found that miR-182-5p expression was significantly higher in prostate cancer tissues compared with normal prostate tissues. We established stable low miR-182-5p expressing cell lines and performed in vivo studies in order to observe potential tumor suppression effects in a xenograft nude mouse model
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