MicroRNA-320c inhibits tumorous behaviors of bladder cancer by targeting Cyclin-dependent kinase 6.
MicroRNA-320c inhibits tumorous behaviors of bladder cancer by targeting Cyclin-dependent kinase 6.
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MicroRNA-320c 通过靶向细胞周期蛋白依赖性激酶 6 抑制膀胱癌的肿瘤行为
DOI：
10.1186/s13046-014-0069-6
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发表时间：
2014-09-02
期刊：
影响因子：
--
通讯作者：
Xie L
中科院分区：
文献类型：
--
作者：
Wang X;Wu J;Lin Y;Zhu Y;Xu X;Xu X;Liang Z;Li S;Hu Z;Zheng X;Xie L
越来越多的证据表明，microRNA (miRNA) 的失调可能导致包括癌症在内的人类疾病。先前的 miRNA 微阵列分析表明 miR-320c 在各种癌症中下调。然而，miR-320c 在人类膀胱癌中的作用尚未得到很好的阐明。因此，本研究旨在探讨miR-320c在人膀胱癌细胞系中的生物学功能和分子机制，探讨其是否可以作为未来膀胱癌的治疗生物标志物。通过定量 RT-PCR 分析了两种人膀胱癌细胞系和 13 名膀胱癌患者的样本中 miR-320c 的表达。通过将模拟物转染至 T24 和 UM-UC-3 来建立 miR-320c 的过表达。通过细胞活力测定、流式细胞术和集落形成测定评估细胞增殖和细胞周期。通过transwell实验评估细胞运动能力。通过荧光素酶测定、定量RT-PCR和蛋白质印迹法确定miR-320c的靶基因。通过蛋白质印迹分析 miR-320c 对细胞周期和迁移率的调节。我们观察到 miR-320c 在人膀胱癌组织以及膀胱癌细胞系 T24 和 UM-UC-3 中下调。 miR-320c 的过表达可诱导 UM-UC-3 和 T24 细胞的 G1 期阻滞，并随后抑制细胞生长。我们还发现 miR-320c 可能会损害 UM-UC-3 和 T24 细胞的运动性。此外，我们确定细胞周期调节因子 CDK6 作为 miR-320c 的新靶点。此外，我们证明 miR-320c 可以通过调节 CDK6 诱导膀胱癌细胞周期停滞和迁移。我们还观察到，在 miR-320c 过表达的膀胱癌细胞中抑制 miR-320c 或恢复 CDK6 部分逆转了 miR-320c 的抑制作用。 miR-320c可通过调节CDK6抑制膀胱癌细胞的增殖、迁移和侵袭。我们的研究表明，miR-320c 未来可能成为膀胱癌的治疗生物标志物。
Increasing 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. Two 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. We 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. miR-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.
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影响因子：
1.6
作者：
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影响因子：
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