Hsiao Kuei-Yang, Lin Ya-Chi, Gupta Sachin Kumar, Chang Ning, Yen Laising, Sun H Sunny, Tsai Shaw-Jenq
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Cancer Res. 2017 May 1;77(9):2339-2350. doi: 10.1158/0008-5472.CAN-16-1883. Epub 2017 Mar 1.
Circular RNA (circRNA) is a class of noncoding 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. 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 colorectal cancer 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. .
环状RNA（circRNA）是一类非编码RNA，其功能大多仍不明确。近期研究表明，circRNA可能参与疾病发病机制，但直接证据稀少。在此，我们阐述了一种新型circRNA——circCCDC66在结直肠癌中的功能作用。来自配对的正常和肿瘤结肠组织样本的RNA测序数据鉴定出众多在癌细胞中特异性上调的circRNA，其中几种通过定量逆转录PCR得到验证。circCCDC66在息肉和结肠癌中表达上调，且与预后不良相关。在结直肠癌细胞系中进行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、侵袭和非锚定依赖性生长。深入研究表明，circCCDC66通过调控一部分癌基因发挥其功能，并且circCCDC66的敲低分别在异种移植和原位小鼠模型中抑制了肿瘤生长和癌症侵袭。综上所述，这些发现突出了circRNA在癌症进展和转移中的一种新型致癌功能。
