Fig. 1
RNA over-editing pattern in protein-coding regions of iCCA genomes is mediated by ADAR1. a The distribution of 12 types of putative protein-coding RNA editing event. b Neighbor preferences (± 10 nucleotide [nt]) of the A-to-I RNA editing sites. A, adenosine; T, thymidine; C, cytosine; G, guanosine; I, inosine. c The percentages of the A-to-I editing sites (present in ≥ 2 samples) with > 10% increase or decrease in variation frequency (VAF) between the iCCA tissues (T) and non-tumor liver tissues (NTL) from the discovery cohort (DISC, n = 15). d-e The mRNA expression levels of ADAR1-p110 and ADAR2 in NTL and T from the patients of DISC cohort (n = 15) assessed by RNA-seq. FPKM, fragments per kilobase of exon model per million reads mapped. e and f The mRNA expression levels of ADAR1-p110 and ADAR2 in non-tumor bile duct tissues (NTBD), NTL and T from the patients of VALI1 cohort assessed by qRT-PCR assays (E), and the patients of Andersen’s cohort (GSE26566) assessed by beadchip (F). g Immunohistochemistry (IHC) analyses of ADAR1 protein levels in NTBD, NTL and T from the patients of VALI2 cohort. Scale bars: top, 300 μm; bottom, 100 μm. The P value was assessed by Wilcox rank sum test. h Immunoblotting assays for ADAR1 and ADAR2 in a panel of cell lines, consisting of one normal intrahepatic biliary epithelial cell line (HIBEpiC) and five types of human iCCA cell line (including IHCC-9810, QBC939, HuCC-T1, RBE and Huh28). i Correlations (Spearman’s rank correlation rho) between the percentages of A-to-I over-editing sites (VAFT-VAFNTL > 10%; present in ≥ 2 samples) and the mRNA expression levels of ADAR1-p110 (left) or ADAR2 (right) in iCCA tissues from the patients of DISC cohort