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筛选差异环状 RNA 表达谱揭示 circTCF25-miR-103a-3p/miR-107-CDK6 通路在膀胱癌中的调控作用。

Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma.

机构信息

The First Clinical College, Chongqing Medical University, Chongqing 400016, China.

Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China.

出版信息

Sci Rep. 2016 Aug 3;6:30919. doi: 10.1038/srep30919.

Abstract

Circular RNAs (circRNAs), a kind of non-coding RNAs, have shown large capabilities in gene regulation. However, the mechanisms underlying circRNAs remain largely unknown so far. Recent studies demonstrated that circRNAs play miRNA sponge effects and regulate gene expression by microRNA response elements. Here, we screened circRNA expression profiles of bladder carcinoma using microarray assay. A total of 469 dysregulated circular transcripts are found in bladder cancer compared with normal tissues, among which 285 were up-regulated and 184 were down-regulated. Six circRNAs were identified to have significant differences by qRT-PCR. We speculated that circRNAs might involve in cancer-related pathways via interactions with miRNA by multiple bioinformatical approaches. Therefore, we further predicted that circTCF25 could sequester miR-103a-3p/miR-107, which potentially lead to the up-regulation of thirteen targets related to cell proliferation, migration and invasion. Subsequently, we demonstrated that over-expression of circTCF25 could down-regulate miR-103a-3p and miR-107, increase CDK6 expression, and promote proliferation and migration in vitro and vivo. This is the first study to exploit circRNA profiling and circRNA/miRNA interactions in bladder cancer. Our work laid the foundation to investigate the functions of circRNAs in cancers. The data also suggest that circTCF25 might be a new promising marker for bladder cancer.

摘要

环状 RNA(circRNAs)是一种非编码 RNA,在基因调控中显示出巨大的能力。然而,到目前为止,circRNAs 的机制还知之甚少。最近的研究表明,circRNAs 发挥 miRNA 海绵效应,并通过 microRNA 反应元件调节基因表达。在这里,我们使用微阵列分析筛选膀胱癌的 circRNA 表达谱。与正常组织相比,膀胱癌中发现了 469 个失调的环状转录物,其中 285 个上调,184 个下调。通过 qRT-PCR 鉴定了 6 个具有显著差异的 circRNAs。我们推测 circRNAs 可能通过与 miRNA 的相互作用,通过多种生物信息学方法参与癌症相关途径。因此,我们进一步预测 circTCF25 可以与 miR-103a-3p/miR-107 结合,从而潜在地上调与细胞增殖、迁移和侵袭相关的十三个靶基因。随后,我们证明 circTCF25 的过表达可以下调 miR-103a-3p 和 miR-107,增加 CDK6 的表达,并促进体外和体内的增殖和迁移。这是首次在膀胱癌中利用 circRNA 图谱和 circRNA/miRNA 相互作用进行研究。我们的工作为研究 circRNAs 在癌症中的功能奠定了基础。该数据还表明 circTCF25 可能是膀胱癌的一个有前途的新标志物。

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