Figure 5.
Comparison of the abnormal gene expression profiles in LCK/R26Tax- and ORP4L-expressing T cells and human ATL T cells. (A) Heat map presentation of RNA-seq data from T cells with or without ORP4L expression from sick B-NDG mice in Figure 3. (B) Heat map presentation of RNA seq data from T cells of 16-month-old WT, LCK/R26Tax, and ORP4Lcko;LCK/R26Tax mice. (C) Venn diagram showing the overlap DEGs of T cells from human ATL, T cells from LCK/R26Tax mice, and T cells with ORP4L expression from the sick B-NDG mice in Figure 3. A total of 51 overlapping genes were identified from the 3 data sets within the Venn diagrams. (D) Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the 51 overlapping genes in panel C. (E-F) PPI network, submodules, and hub genes. (E) The PPI network of 51 overlapping genes and clustering module (MCODE score, 15.333). Yellow circles represent hub genes. (F) Important degree of genes in the clustering modules, according to multiple consensus clustering analysis methods by the CytoHubba application. The darker the color, the more important it is. (G) Expression of p53 downstream targeting genes CCNB1, CCNB2, and RRM2 in normal human T cells and patients with ATL T cells. The data are from the literature (Pise-Masison et al33). Mean ± standard deviation (SD; n = 7 normal specimens; n = 19 specimens from patient with ATL; Student t test). (H-I) qPCR (H) and western blot (I) analyses of the expression of CCNB1, CCNB2, and RRM2 in patients with ATL (ATL 13, 16, 19, 23, 25, and 30) T cells subjected to ORP4L knockdown or p53 inhibitor PFTα. Patients with ATL T cells were transfected with ORP4L shRNA for 72 hours or treated with 50 μM PFTα for 24 hours. Mean ± SD (n = 3 normal specimens, n = 6 specimens from patient with ATL for qPCR; Student t test). (J) qPCR analysis the expression of CCNB1, CCNB2, and RRM2 in LCK/R26Tax T cells subjected to ORP4L knockdown or p53 inhibitor PFTα. T cells were transfected with ORP4L shRNA for 72 hours or treated with 50 μM PFTα for 24 hours. Mean ± SD (n = 4 mice of each group; Student t test). (K) qPCR analysis the expression of CCNB1, CCNB2, and RRM2 in T cells, with or without ORP4L expression from the sick B-NDG mice in Figure 3. T cells were transfected with ORP4L shRNA for 72 hours or treated with 50 μM PFTα for 24 hours. Mean ± SD (n = 4 mice of each group; Student t test). ***P < .001.