Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma.
Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma.
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DOI：
10.1038/srep30919
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发表时间：
2016-08-03
影响因子：
4.6
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Zhong Z;Lv M;Chen J
环状RNA（circRNA）是一种非编码RNA，在基因调控方面表现出强大的能力。然而，到目前为止，circRNA 的潜在机制仍然很大程度上未知。最近的研究表明，circRNA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了膀胱癌的circRNA表达谱。与正常组织相比，膀胱癌中总共发现了469个失调的环状转录本，其中285个上调，184个下调。 qRT-PCR 鉴定出 6 个 circRNA 存在显着差异。我们推测，circRNA 可能通过多种生物信息学方法与 miRNA 相互作用，参与癌症相关通路。因此，我们进一步预测circTCF25可以隔离miR-103a-3p/miR-107，这可能导致与细胞增殖、迁移和侵袭相关的13个靶标的上调。随后，我们证明了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。这是第一项在膀胱癌中利用 circRNA 分析和 circRNA/miRNA 相互作用的研究。我们的工作为研究 circRNA 在癌症中的功能奠定了基础。数据还表明 circTCF25 可能是膀胱癌新的有前景的标记物。
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.