Chromatin accessibility analysis uncovers TFAP2A as a regulator on pro-angiogenesis of acquired resistance to anlotinib

Anlotinib, a multitarget agent a multi-target agent that inhibits tumor proliferation and angiogenesis, has been demonstrated to be effective for non-small cell lung cancer (NSCLC) at third-line or over third-line. However, the underlying mechanisms of anlotinib acquired-resistance is still unclear. Here we performed chromatin accessibility profiling on anlotinib-resistant NCI-H1975 and wild-type NCI-H1975. By integrating with transcriptome analysis, we found that anlotinib resistance was due to increased angiogenic capacity, and revealed that TFAP2A was involved in anlotinib resistance. Next, TFAP2A was knock-down in anlotinib-resistant cells and RNAseq was performed to see down-regulated genes with TFAP2A KD. Anlotinib-resistant and wild-type NCI-H1975 cells were used for ATAC-seq and RNA-seq, TFAP2A KD anlotinib-resistant cells were used for RNAseq.