Laboratory of Molecular and Genetic Information, Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Laboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
EMBO Rep. 2019 Aug;20(8):e47052. doi: 10.15252/embr.201847052. Epub 2019 Jul 29.
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.
长链非编码 RNA（lncRNA）在许多疾病条件下表达异常，包括癌症。越来越多的证据表明，一些 lncRNA 可能在癌症的进展和转移中发挥关键作用。在这里，我们鉴定了一组在体内分离的结肠癌 HCT116 细胞的转移亚群中上调的 lncRNA，并且表明这些 lncRNA 中的一种，我们将其命名为 CALIC，是结肠癌细胞转移活性所必需的。我们表明，CALIC 与 RNA 结合蛋白 hnRNP-L 结合，并赋予 hnRNP-L 介导的基因表达特异性。此外，我们证明 CALIC/hnRNP-L 复合物上调酪氨酸激酶受体 AXL，并且使用 shRNA 在结肠癌细胞中敲低 CALIC 或 AXL 会削弱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能。
