C-Myc-activated long noncoding RNA CCAT1 promotes colon cancer cell proliferation and invasion
C-Myc-activated long noncoding RNA CCAT1 promotes colon cancer cell proliferation and invasion
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C-Myc激活的长非编码RNA CCAT1促进结肠癌细胞增殖和侵袭
DOI：
10.1007/s13277-014-2526-4
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发表时间：
2014-12-01
期刊：
影响因子：
--
通讯作者：
Fan, Zhining
中科院分区：
文献类型：
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作者：
He, Xiaolu;Tan, Xueming;Fan, Zhining
近年来，越来越多的证据表明，长链非编码rna （lncRNAs）参与了人类肿瘤的发生，并在包括结肠癌在内的许多癌症中发生了失调。LncRNA可以通过其组织特异性调节肿瘤发生和发展的重要途径，这表明LncRNA将成为有价值的生物标志物和治疗靶点。结肠癌相关转录本1 （CCAT1）是一个2628个核苷酸的lncrna，位于一个众所周知的转录因子c-Myc附近。CCAT1已被发现在许多癌症中表达上调，包括胃癌和结肠腺瘤癌。然而，它在结肠癌中的作用仍未得到充分证明，需要进一步研究。在本研究中，我们旨在探讨CCAT1的预后价值和生物学功能，并发现哪些因素可能有助于结肠癌中CCAT1的失调。我们的研究结果显示，CCAT1在结肠癌组织中较正常组织明显过表达，其表达升高与患者的临床分期、淋巴结转移及术后生存时间有关。此外，c-Myc可通过直接结合CCAT1的启动子区促进CCAT1的转录，在结肠癌细胞中上调CCAT1的表达可促进细胞增殖和侵袭。这些数据表明，c- myc激活的lncRNA CCAT1表达有助于结肠癌的肿瘤发生和转移过程，可以预测结肠癌的临床结局，是lncRNA直接治疗的潜在靶点。
Recently, more and more evidence are rapidly accumulating that long noncoding RNAs (lncRNAs) are involved in human tumorigenesis and misregulated in many cancers, including colon cancer. LncRNA could regulate essential pathways that contribute to tumor initiation and progression with their tissue specificity, which indicates that lncRNA would be valuable biomarkers and therapeutic targets. Colon cancer-associated transcript 1 (CCAT1) is a 2628 nucleotide-lncRNA and located in the vicinity of a well-known transcription factor c-Myc. CCAT1 has been found to be upregulated in many cancers, including gastric carcinoma and colonic adenoma-carcinoma. However, its roles in colon cancer are still not well documented and need to be investigated. In this study, we aim to investigate the prognostic value and biological function of CCAT1 and discover which factors may contribute to the deregulation of CCAT1 in colon cancer. Our results revealed that CCAT1 was significantly overexpressed in colon cancer tissues when compared with normal tissues, and its increased expression was correlated with patients’ clinical stage, lymph nodes metastasis, and survival time after surgery. Moreover, c-Myc could promote CCAT1 transcription by directly binding to its promoter region, and upregulation of CCAT1 expression in colon cancer cells promoted cell proliferation and invasion. These data suggest that c-Myc-activated lncRNA CCAT1 expression contribute to colon cancer tumorigenesis and the metastatic process and could predict the clinical outcome of colon cancer and be a potential target for lncRNA direct therapy.