PDE4D and lung cancer: These individual CRTC knockout cells showed a reduction in expression of several CREB-mediated target genes, such as PDE4D, INSL4, LINC00473, and NR4A2, but not to the extent of their endogenous levels in LKB1-wt lung cancer H522 cells, as assayed by western blotting or RT-qPCR assays (Figure 2A,B).