Fig. 5

Phosphatidylinositol-4-phosphate 5-kinase type 1 gamma (PIP5K1C) knockdown or pharmacologic inhibition reduces TNBC growth. A The effect of siRNA-mediated PIP5K1C knockdown on cell growth of two TNBC cell lines was assessed in WST-1 assays (n = 6; mean ± SD; *p ≤ 0.05; ***p ≤ 0.005). B SUM159 and MDA-MB-231 cells were transiently transfected with 20 nM PIP5K1C siRNA or control and seeded at low density to observe colony formation after 7 (SUM159) or 14 days (MDA-MB-231). Absolute numbers of colonies (as seen in the representative images on the right) were counted and are presented as mean ± SD (on the left) (n = 6; **p ≤ 0.01). C Overall survival of breast cancer patients split into a PIP5K1C low (black; n = 19) and high (red; n = 46) group based on protein levels from proteomic data (log-rank test; p = 0.0097; Hazard Ratio (HR) = 3.72; confidence interval 1.28–10.8). D Overall survival of TNBC patients split into a PIP5K1C low (black; n = 47) and high (red; n = 106) expression group (log-rank test; p = 0.1; Hazard ratio (HR) = 1.98; confidence interval 0.86 – 4.54) and relapse-free survival of TNBC patients split into a PIP5K1C low (black; n = 272) and high (red; n = 120) expression group (log-rank test; p = 0.0091; Hazard ratio (HR) = 1.64; confidence interval 1.13–2.38), based on gene chip expression data. E RNA-seq-based expression data of PIP5K1C in paired breast cancer (red; n = 112) and normal adjacent tissue (green; n = 112) (p = 0.0258; Mann–Whitney-U-Test). F SUM159 and MDA-MB-231 cells were transiently transfected with miR-4649-5p or mimic control and treated with 10 μM of the PIP5K1C inhibitor UNC3230 or DMSO as vehicle control. Effects on cell growth were analyzed in WST-1 assays (n = 6; mean ± SD; **p ≤ 0.01, ***p ≤ 0.005, compared by One-way ANOVA and Tukey multiple comparison test)