Abstract
BackgroundIncreasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to human disease including cancer. Previous miRNA microarray analysis illustrated that miR-320c is down-regulated in various cancers. However, the roles of miR-320c in human bladder cancer have not been well elucidated. Therefore, this study was performed to investigate the biological functions and molecular mechanisms of miR-320c in human bladder cancer cell lines, discussing whether it could be a therapeutic biomarker of bladder cancer in the future.MethodsTwo human bladder cancer cell lines and samples from thirteen patients with bladder cancer were analyzed for the expression of miR-320c by quantitative RT-PCR. Over-expression of miR-320c was established by transfecting mimics into T24 and UM-UC-3. Cell proliferation and cell cycle were assessed by cell viability assay, flow cytometry and colony formation assay. Cell motility ability was evaluated by transwell assay. The target gene of miR-320c was determined by luciferase assay, quantitative RT-PCR and western blot. The regulation of cell cycle and mobility by miR-320c was analyzed by western blot.ResultsWe observed that miR-320c was down-regulated in human bladder cancer tissues and bladder cancer cell lines T24 and UM-UC-3. Over-expression of miR-320c could induce G1 phase arrest in UM-UC-3 and T24 cells, and subsequently inhibited cell growth. We also indentified miR-320c could impair UM-UC-3 and T24 cell motility. In addition, we identified CDK6, a cell cycle regulator, as a novel target of miR-320c. Moreover, we demonstrated miR-320c could induce bladder cancer cell cycle arrest and mobility via regulating CDK6. We also observed that inhibition of miR-320c or restoration of CDK6 in miR-320c-over-expressed bladder cancer cells partly reversed the suppressive effects of miR-320c.ConclusionsmiR-320c could inhibit the proliferation, migration and invasion of bladder cancer cells via regulating CDK6. Our study revealed that miR-320c could be a therapeutic biomarker of bladder cancer in the future.
Highlights
Increasing evidence has suggested that dysregulation of microRNAs could contribute to human disease including cancer
We used realtime RT-PCR to quantify the expression levels of miR320c in 13 pairs of human bladder cancer tissues and non muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) was shown in a box and whiskers graph
The expression level of miR-320c was significantly lower in MIBC compared with NMIBC. (C) The miR-320c levels in 4 bladder cancer cell lines were lower compared with SV-HUC-1 cell line
Summary
Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to human disease including cancer. This study was performed to investigate the biological functions and molecular mechanisms of miR-320c in human bladder cancer cell lines, discussing whether it could be a therapeutic biomarker of bladder cancer in the future. MicroRNAs (miRNAs) are small (20 ~ 23 nucleotides), endogenous, non-coding RNAs, which constitute a novel cluster of target gene regulators [6]. They are involved in various cellular processes, including self-renewal, proliferation, metabolism and apoptosis, by inducing post-transcriptional gene repression via accelerating the degradation and/or blocking the translation of their target mRNAs [7]. The miRNA genes were observed to be deleted in leukemia initially illustrated the important role of miRNA in carcinogenesis [8]. The initial study of miRNA expression in bladder cancer was reported by Gottardo in 2007 and 10 up-regulated miRNAs were detected [15]
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