Fig 2: Coordinated expression of FoxM1 and STMN1 in cancers. a Analysis of the mRNA levels of FoxM1 and STMN1 (cancer vs. normal) in multiple solid cancers from Oncomine Database. b The expression of FoxM1 and STMN1 in hepatocellular carcinoma cohorts (GSE14520, GSE14323), gastric cancer cohorts (GSE13911, GSE19826, GSE27342) and colon cancer cohorts (GSE8671). The data were presented as the mean ± SD of different samples. The significance was analyzed by the Student’s t-test. **P < 0.01, ***P < 0.001, ****P < 0.0001. c The correlation of FoxM1 and STMN1 expression in 31 solid tumors (including ACC, BLCA, BRCA, CESC, CHOL, COAD, ESCA, GBM, HNSC, KICH, KIRC, KIRP, LGG, LIHC, LUAD, LUSC, MESO, OV, PAAD, PCPG, PRAD, READ, SARC, SKCM, STAD, TGCT, THCA, THYM, UCEC, UCS and UVM) from the TCGA database was analyzed using the GEPIA platform, and the correlation of FoxM1 and STMN1 expression in LIHC (n = 373), GC (n = 415) and CRC (n = 328) TCGA data. d Protein levels of FoxM1 and STMN1 in LIHC (n = 79), GC (n = 61) and CRC (n = 68) were analyzed by IHC. The correlation of FoxM1 and STMN1 was analyzed by linear regression analysis

Fig 3: E2F1 transactivates stathmin1 and TACC3 in CRC cells. A Schematic representations of the promoter regions of human STMN1 and TACC3. The predicted E2F1 binding sites are indicated. B Agarose gel electrophoresis of ChIP-PCR products in the input, IgG, and ChIP groups, showing that E2F1 interacted with the STMN1 promoter at P3, and with the TACC3 promoter at P2/P3. C Quantitative PCR analysis of the efficiency of interaction of E2F1 DNA at the promoter sites shown in B. D Luciferase activities of DLD1 cells transfected with pGP4.19 promoters carrying wild-type and mutant binding sites promoter, pRL-TK and vector/E2F1

Fig 4: The expression of STMN1 protein in human prostatic tissues. A–H Representative immunohistochemical staining of STMN1 in human prostatic tissues. A Positive STMN1 staining was observed in basal epithelial cells in benign prostatic tissue. B–G Varying intensity of STMN1 staining were present in luminal and/or basal epithelial cells in adenocarcinoma tissues. The # symbol and arrowhead indicated basal epithelial cells and luminal epithelial cells, respectively. H and I Serial sections of a NEPC tumor showed STMN1 expression in the NEPC area (highlighted by the expression of NEPC marker, INSM1) but no expression was detected in adjacent AdPC cells. J Distribution of STMN1 expression (Allred score) among prostate specimens, demonstrating an association between STMN1 expression and Gleason Score of PCa. (Spearman correlation: 0.73, p < 0.01). K Dual immunofluorescence staining to access the co-expression STMN1 with NEPC marker Chromogranin A (CHGA) in AdPC tumor with NE differentiation. STMN1 expression was detected in both NE (arrowheads) and non-NE (arrows) cells. Scale bars = 20 μm

Fig 5: CARMA3 regulated the expression of STMN1 via the NF-κB pathway. A, Reverse-transcription polymerase chain reaction (RT-PCR) analysis of the STMN1 expression level in CARMA3-shRNA-knockdown clear cell renal cell carcinoma (ccRCC) cells. B, Western blot analysis of the IκBα phosphorylation level in CARMA3-shRNA-knockdown ccRCC cells. C, RT-PCR analysis of the STMN1 expression level after application of the pyrrolidinedithiocarbamic acid NF-κB inhibitor. D, Luciferase assays of the NF-κB1 transcription activity between the wild-type and mutated STMN1 promotors. *P < 0.05, **P < 0.01 and ***P < 0.001.