Noncoding Effects of Circular RNA CCDC66 Promote Colon Cancer Growth and Metastasis.
Noncoding Effects of Circular RNA CCDC66 Promote Colon Cancer Growth and Metastasis.
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DOI：
10.1158/0008-5472.can-16-1883
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发表时间：
2017-05-01
期刊：
影响因子：
11.2
通讯作者：
Tsai SJ
中科院分区：
文献类型：
--
作者：
Hsiao KY;Lin YC;Gupta SK;Chang N;Yen L;Sun HS;Tsai SJ
环状RNA（circRNA）是一类非编码RNA，其功能大多未知。最近的研究表明circRNA可能参与疾病发病机制，但直接证据很少。在这里，我们描述了一种新型 circRNA circCCDC66 在结直肠癌 (CRC) 中的功能作用。来自匹配的正常和肿瘤结肠组织样本的 RNA-Seq 数据鉴定出许多在癌细胞中特异性升高的 circRNA，其中一些通过定量 RT-PCR 得到了验证。 CircCCDC66 表达在息肉和结肠癌中升高，并且与不良预后相关。 CRC 细胞系的功能获得和功能丧失研究表明，circCCDC66 控制多种病理过程，包括细胞增殖、迁移、侵袭和不依赖贴壁的生长。深入的表征表明，circCCDC66 通过调节一部分癌基因发挥其功能，敲低 circCCDC66 分别可抑制异种移植和原位小鼠模型中的肿瘤生长和癌症侵袭。总而言之，这些发现强调了 circRNA 在癌症进展和转移中的一种新的致癌功能。
Circular RNA (circRNA) is a class of non-coding RNA whose functions remain mostly unknown. Recent studies indicate circRNA may be involved in disease pathogenesis, but direct evidence is scarce. Here we characterize the functional role of a novel circRNA, circCCDC66, in colorectal cancer (CRC). RNA-Seq data from matched normal and tumor colon tissue samples identified numerous circRNAs specifically elevated in cancer cells, several of which were verified by quantitative RT-PCR. CircCCDC66 expression was elevated in polyps and colon cancer and was associated with poor prognosis. Gain-of-function and loss-of-function studies in CRC cell-lines demonstrated that circCCDC66 controlled multiple pathological processes, including cell proliferation, migration, invasion, and anchorage-independent growth. In-depth characterization revealed that circCCDC66 exerts its function via regulation of a subset of oncogenes, and knockdown of circCCDC66 inhibited tumor growth and cancer invasion in xenograft and orthotopic mouse models, respectively. Taken together, these findings highlight a novel oncogenic function of circRNA in cancer progression and metastasis.