Abstract
BackgroundAn increasing number of studies have demonstrated that deregulation of microRNAs (miRNAs) was a common event in tumor tissues and miRNAs would be treated as ideal tumor biomarkers or therapeutic targets. miR-195-5p (termed as miR-195 for briefly in the following part) was suggested to function as a tumor suppressor in cancer development and progression. However, the roles of miR-195 in human prostate cancer are still elusive. Thus, this study was performed to investigate the biological functions and its molecular mechanisms of miR-195 in human prostate cancer cell lines, discussing whether it has a potential to be a therapeutic way of prostate cancer.MethodsTwo human prostate cancer cell lines were analyzed for the expression of miR-195 by quantitative real-time reverse transcription–polymerase chain reaction (RT–PCR). A gain-of-function study of miR-195 was conducted by transfecting mimics into DU145 and PC3 cells and cell motility and invasion ability were evaluated by wound healing assay and transwell assay. Tissue microarray, and immunohistochemistry with antibodies against Fra-1 was performed using the peroxidase and DAB methods. The target gene of miR-195 was determined by luciferase assay, quantitative RT–PCR and western blot. The regulation of motility by miR-195 was analyzed by western blot.ResultsmiR-195 was frequently down-regulated in both prostate cancer cell lines, DU145 and PC3. Overexpression of miR-195 significantly repressed the capability of migration and invasion of prostate cancer cells. In addition, we identified Fra-1, a cell motility regulator, as a novel target of miR-195. Fra-1 was up-regulated in prostate cancer tissues. We also observed that inhibition of miR-195 or restoration of Fra-1 in miR-195-over-expressed prostate cancer cells partially reversed the suppressive effects of miR-195. Furthermore, we demonstrated miR-195 could inhibit prostate cancer cell motility by regulated the expression of c-Met, MMP1, MMP9.ConclusionsmiR-195 can repress the migration and invasion of prostate cancer cells via regulating Fra-1. Our results indicate that miR-195 could be a tumor suppressor and may have a potential to be a diagnostics or therapeutic target in prostate cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0650-6) contains supplementary material, which is available to authorized users.
Highlights
Introduction of miR195 inhibited migration and invasion of prostate cancer cells in vitro To elucidate that whether miR-195 could function as a tumor suppressor, the effects of miR-195 over-expression was evaluated in vitro
Our results indicate that miR-195 could be a tumor suppressor and may have a potential to be a diagnostics or therapeutic target in prostate cancer
Numerous cellular processes are affected by miRNA, including differentiation, proliferation, cellcycle control, apoptosis, migration and invasion [4]. miRNAs exert their regulatory effects by binding to partially complementary sequences in the 3′-untranslated region (3′UTR) of target mRNAs, reducing the stability and/or translation efficiency of target mRNAs in a sequencespecific manner
Summary
195 inhibited migration and invasion of prostate cancer cells in vitro To elucidate that whether miR-195 could function as a tumor suppressor, the effects of miR-195 over-expression was evaluated in vitro. The data was shown in additional file 2: Figure S1, which provide evidence to conclude that miR-195 suppresses cell motility Taken together, these results revealed that miR-195 negatively modulate prostate cancer cells migration and invasion. Accumulating evidence suggests that miRNAs are significant molecules in diverse cancers, including prostate cancer, by regulating the expression of various oncogenes and tumor suppressors [5, 6]. Two promising miRNAs, miR-141 and miR-375, were suggested as diagnostic and prognostic marker across independent studies Both miRNAs were found to be elevated in serum of men with metastatic castration-resistant prostate cancer compared to healthy individuals [12, 13]. The study of miRNAs is still challenging due to variable downstream regulators, the above evidence gives us a promising outlook for the application of miRNAs for prostate cancer management
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