The long noncoding RNA CASC2 functions as a competing endogenous RNA by sponging miR-18a in colorectal cancer.
The long noncoding RNA CASC2 functions as a competing endogenous RNA by sponging miR-18a in colorectal cancer.
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DOI：
10.1038/srep26524
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发表时间：
2016-05-20
影响因子：
4.6
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Huang G;Wu X;Li S;Xu X;Zhu H;Chen X
最近的证据强调了长链非编码RNA（lncRNA）在肿瘤生物学中的重要调控作用。在结直肠癌（CRC）中，几种lncRNA的表达失调，并在CRC肿瘤发生中发挥重要作用。然而，新的人类lncRNA，CASC 2（癌症易感性候选者2），在肿瘤生物学中的潜在生物学作用和调控机制知之甚少。在这项研究中，CRC组织和CRC细胞系中CASC 2表达显着降低，并且晚期肿瘤淋巴结转移期疾病（TNM III和IV）患者中表达降低的频率显着更高（P = 0.028）。进一步的功能实验表明，CASC 2可以通过充当miR-18 a的竞争性内源RNA（ceRNA）来直接上调PIAS 3表达。这种相互作用导致STAT 3下游基因的去抑制，并通过延长G 0/G1-S相变在体外和体内抑制CRC细胞增殖和肿瘤生长。综上所述，这些观察结果表明CASC 2作为ceRNA在CRC发病机制中起重要作用，并可作为癌症诊断和治疗的潜在靶点。
Recent evidence highlights the crucial regulatory roles of long noncoding RNAs (lncRNA) in tumor biology. In colorectal cancer (CRC), the expression of several lncRNAs is dysregulated and play essential roles in CRC tumorigenesis. However, the potential biological roles and regulatory mechanisms of the novel human lncRNA, CASC2 (cancer susceptibility candidate 2), in tumor biology are poorly understood. In this study, CASC2 expression was significantly decreased in CRC tissues and CRC cell lines, and decreased expression was significantly more frequent in patients with advanced tumor-node-metastasis stage disease (TNM III and IV) (P = 0.028). Further functional experiments indicate that CASC2 could directly upregulate PIAS3 expression by functioning as a competing endogenous RNA (ceRNA) for miR-18a. This interactions leads to the de-repression of genes downstream of STAT3 and consequentially inhibition of CRC cell proliferation and tumor growth in vitro and in vivo by extending the G0/G1-S phase transition. Taken together, these observations suggest CASC2 as a ceRNA plays an important role in CRC pathogenesis and may serve as a potential target for cancer diagnosis and treatment.