Figure 3. Disrupting either histone binding or SRA domains of UHRF1 exerts profound anti-tumor effects both in vitro and in vivo.

(A) Soft agar assays showing colony formation of the HCT116 (left) and RKO (right) cells expressing the representative domain mutants simultaneously with endogenous UHRF1 depletion. Quantitative measurements of the percentage of colony area for indicated domain mutants with endogenous UHRF1 depletion compared to Mock are shown in bar plots. Data are represented as mean ± SD (n = 3).

(B) Competition-based proliferation assays for HCT116 (upper) and RKO (lower) cells expressing both the indicated domain mutants and the GFP-shRNA targeting endogenous UHRF1, co-cultured with the Mock-treated cells. The percentages of the GFP⁺ cells are tacked and normalized to the percentages at day 2. Data are represented as mean ± SD (n = 3).

(C) Tumor volumes of mice xenografts are plotted with time after injecting HCT116 (left) and RKO (right) cells expressing the indicated domain mutants simultaneously with endogenous UHRF1 depletion. Data are represented as mean ± SEM (n = 5). The mark “x” indicates the stopped observation for the experimental group where at least one mouse was sacrificed due to the tumor volume exceeding 2000 mm³.

(D) Tumor volumes of mice xenografts at week 6 from (C) are compared to Mock tumors. Data are represented as mean ± SEM (n = 5). p values are determined using a two-tailed t-test (****p < 0.0001, n.s., not significant).

See also Figure S3