Fig. 8

FTO-IT1/FTO signaling promoted proliferation of HCC cells in vivo and correlated with poor clinical outcomes. A-C Subcutaneous implantation mouse models were established by using MHCC97H cells that were transfected with lentivirus containing siFTO-IT1 plasmid and/or overexpression FTO plasmid. Growth curve (A), tumor weight (B) and representative images (C) of xenografts (n = 5) in the three treatment groups for 28 days were shown. D Representative HE and IHC staining for FTO, GLUT1, PKM2 and Ki67 expression in the subcutaneous xenografts. The xenografts were collected 4 weeks after tumor implantation. E, F The relative expression of FTO-IT1 (E) and FTO mRNA (F) was detected in 92 pairs HCC clinical specimens and matched paracancerous tissues by qRT-PCR. NT: non-tumor. G The expression correlation between FTO-IT1 and FTO in 92 pairs HCC clinical specimens and matched paracancerous tissues. NT: non-tumor. H Kaplan–Meier curves showed OS of 92 HCC patients with high or low FTO-IT1 expression. I Kaplan–Meier curves showed OS of 92 HCC patients with high or low FTO expression. J 92 HCC patients were divided into three groups based on the expression level of FTO-IT1 and FTO as indicated. OS of those patients was evaluated via Kaplan–Meier analysis. K ROC curve analysis for OS for FTO-IT1 (P = 0.023), FTO (P = 0.029) as individual biomarkers or for the combined panel (P = 0.004). Setting parameters were as follows: death as positive event; score of high FTO-IT1 or FTO samples was 1, while low FTO-IT1 or FTO samples was 0. Score of the combined panel was the sum of the scores of each sample. Area under the curve (AUC) was used to evaluate predictive capability. L The representative IHC images of FTO, GLUT1, PKM2 and c-Myc in 92 HCC tissues with high or low levels of FTO-IT1. Scale bar, 100/25 μm. M Schematic illustration of FTO-IT1/FTO/c-Myc axis maintaining the malignancy of HCC