Fig. 3: Loss of UHRF1 leads to apoptosis in cells expressing oncogenic KRAS cells.

a Flow cytometry of KRAS mutant (H2009) and KRAS wild-type (H1437) cells expressing Cas9 and transduced with lentiviral vectors expressing the indicated sgRNAs. Cells were co-stained with Annexin V-APC and propidium iodide (PI). b Quantification of apoptosis in a panel of lung cancer cell lines. Red bars – KRAS mutant cells (H2009, H358, H23); gray bars – KRAS wt cells (H1568, H1437, H1299). Bars represent means of n = 3 of biological replicates; **p = 0.007954, ***p = 0.000206, not significant (ns) p > 0.05 by anova followed by Dunnett’s multiple comparisons test between the indicated UHRF1 sgRNA and the control sgRNA. c Images of spheroids from H358 cells expressing Cas9 and the indicated sgRNAs treated with either DMSO or 4 nM of Sotorasib. d Quantification of spheroid area in two cell lines (left – H358, right – A549) expressing Cas9 and the indicated sgRNAs. Cells were treated with DMSO, 10 nM of DNMT1i GSK3685032, 4 nM of Sotorasib, 3 nM of MEKi Trametinib, or 15 nM of PI3Ki Copanlisib. Bars represent mean of n = 4 (H358 sgNeg+DMSO, H358 sgUHRF1+DMSO), n = 3 (A549 sgNeg+DMSO, A549 sgUHRF1+DMSO), or n = 1 biological replicates (all remaining conditions) performed in n = 3 technical replicates. Bars represent means and are presented as fold change relative to control (sgNeg); *p < 0.05, **p < 0.01, ***p < 0.001, ns - not significant by unpaired two-sided Student’s t test. Source data are provided as a Source data file.