Fig 2: TRIB2 expression in Cisplatin-resistant SCLC cells(A) Volcano plot showing the relationship between the statistical p-values and the gene expression change ratio of CRSC vs. H69 cells in microarray analysis. (B) TRIB2 mRNA expression in H69 cells and SCLC cells from the three Cisplatin-treated mice. (C) TRIB2 protein in H69 cells and SCLC cells from the Cisplatin-treated mice. (TRIB2 gene indicated with arrow. (**, P < 0.01 vs. H69).

Fig 3: TRIB2 and CEBPA proteins in SCLC patients(A) Patient 1: CT scan before and two months after Cisplatin treatment. (B) Patient 2: CT scan before and two months after Cisplatin treatment. (Arrows indicate tumor.) (C) Tumor sample from the Cisplatin-sensitive Patient 1 did not express TRIB2 protein. (D) Tumor sample from the Cisplatin-resistant Patient 2 presented high levels of TRIB protein in the cytoplasm and nucleus of tumor cells. (E) Tumor sample from Patient 1 demonstrated CEBPA protein in the nucleus of the tumor cells. (F) Tumor sample from the Patient 2 did not have detectable CEBPA protein levels.

Fig 4: TCF3 binds to TRIB2 regulatory elements and activates transcription. A Motif enrichment analysis was performed on tissue-specific promoter and enhancer regions. B Intersection of HB-specific promoter motifs and up-regulated genes, showing significant P-values for related TFs. C Correlation analysis between TCF3 and TRIB2 expression in HB datasets (GSE132219 and GSE104766). D TCF3 and TRIB2 expression in datasets GSE132219 (n = 43 HB and 46 non-tumor samples) and GSE104766 (n = 23 HB and 23 non-tumor samples), respectively. E qRT-PCR analysis of TRIB2 in HepG2 cells with or without TCF3 knockdown (n = 3 independent biological replicates). F-G Western blots of TRIB2, NRF2, HO-1, NQO1 (F), and 4-HNE (G) in HepG2 cells with or without TCF3 knockdown. H Identification of TCF3-binding motif within TRIB2 promoter using JASPAR database. I Schematic of the TRIB2 promoter showing TCF3-binding sites and mutation design. J Luciferase reporter assays showing TRIB2 promoter activity regulated by TCF3 overexpression, knockdown, or binding site mutation (n = 3 independent biological replicates). K ChIP-qPCR assays suggested the occupancy of TCF3 at TRIB2 promoter (left) and enhancer (right) elements (n = 3 independent biological replicates)