The novel lncRNA CALIC upregulates AXL to promote colon cancer metastasis
The novel lncRNA CALIC upregulates AXL to promote colon cancer metastasis
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DOI：
10.15252/embr.201847052
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发表时间：
2019-07-29
期刊：
影响因子：
7.7
通讯作者：
Akiyama, Tetsu
中科院分区：
文献类型：
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作者：
Kawasaki, Yoshihiro;Miyamoto, Masaya;Akiyama, Tetsu
长链非编码RNA（lncRNA）在包括癌症在内的许多疾病中异常表达。越来越多的证据表明，一些lncRNA可能在癌症的进展和转移中起关键作用。在这里，我们鉴定了一组在体内从结肠癌HCT 116细胞分离的转移性亚群中上调的lncRNA，并表明其中一种lncRNA，我们将其命名为CALIC，是结肠癌细胞转移活性所必需的。我们发现，CALIC协会与RNA结合蛋白hnRNP-L，并赋予特异性hnRNP-L介导的基因表达。此外，我们证明了CALIC/hnRNP-L复合物上调酪氨酸激酶受体AXL，并且在结肠癌细胞中使用shRNA敲低CALIC或AXL减弱了它们在小鼠中形成转移的能力。这些结果表明，CALIC/hnRNP-L复合物增强了结肠癌细胞的转移潜力。
Long non-coding RNAs (lncRNAs) are aberrantly expressed in many disease conditions, including cancer. Accumulating evidence indicates that some lncRNAs may play critical roles in cancer progression and metastasis. Here, we identify a set of lncRNAs that are upregulated in metastatic subpopulations isolated from colon cancer HCT116 cells in vivo and show that one of these lncRNAs, which we name CALIC, is required for the metastatic activity of colon cancer cells. We show that CALIC associates with the RNA-binding protein hnRNP-L and imparts specificity to hnRNP-L-mediated gene expression. Furthermore, we demonstrate that the CALIC/hnRNP-L complex upregulates the tyrosine kinase receptor AXL and that knockdown of CALIC or AXL using shRNA in colon cancer cells attenuates their ability to form metastases in mice. These results suggest that the CALIC/hnRNP-L complex enhances the metastatic potential of colon cancer cells.