LacZ lentiviral particles

Long noncoding RNAs (lncRNAs) are aberrantly expressed in many disease conditions, including cancer. Accumulating evidence suggests that some lncRNAs may play key roles in cancer progression and metastasis. Here, researchers identified a set of lncRNAs that are upregulated in a metastatic subpopulation isolated from colon cancer HCT116 cells in vivo and showed that one of these lncRNAs (CALIC) is required for the metastatic activity of colon cancer cells. The study showed that CALIC associates with the RNA-binding protein hnRNP-L and confers specificity to hnRNP-L-mediated gene expression. Furthermore, 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.

To evaluate the synergistic role of CALIC and hnRNP-L in AXL expression, researchers generated lentiviruses expressing wild-type CALIC (CALIC-full), CALIC-mut, or a deletion mutant CALIC lacking the hnRNP-L binding region (CALIC-296-913). Lentivirus encoding LacZ was used as a control. AXL expression was significantly enhanced in HCT116 cells infected with lentivirus carrying CALIC-full compared with control cells (Figure 1A). In contrast, AXL expression was not enhanced in HCT116 cells infected with lentivirus carrying CALIC-mut or CALIC-296-913. These results suggest that CALIC and hnRNP-L synergistically induce AXL expression in HCT116 cells. On the other hand, in Caco-2 cells, which express low levels of CALIC, AXL expression was not increased by CALIC-full (Figure 1B and C). Thus, AXL expression may be regulated in a cell type-specific manner. The expression levels of other factors, including hnRNP-L, may be important for AXL expression.

Figure 1. Expression analysis of AXL and CALIC. (Kawasaki Y, et al., 2019)