Fig. 4
Tissue-specific miRNA expression results in differential p53 deregulation. a The A (TP53A) to C (in red, TP53C) variation creates a miR-382 (hsa-miR-382-5p) site and compromises the miR-325 (hsa-miR-325-3p) site. b miR-325:miR-382 expression ratio in different human tissues, calculated by dividing the mean miR-325 read count by the mean miR-382 read count, using deep-sequencing data obtained from miRGator. c miR-325:miR-382 expression ratio in different mouse tissues using qPCR. d miR-325:miR-382 expression ratio in the indicated human cancer cell lines using qPCR. The data in (c, d) were presented as mean ± s.e.m.; error bars depict s.e.m. n = 3 biological triplicates for each cell line with three technical triplicates. e Representative western blotting analysis for p53 in human cell lines. f p53 expression (top) and reporter activity (bottom) in p53+/+ and p53C/C MEFs transfected with miR-325 or miR-382 inhibitors or mimics. Control denotes the negative control #1 for mirVana miRNA inhibitors or mimics; Rel. ratio: the relative signal density of p53 as referenced to GAPDH (values were the average of three independent experiments). *P < 0.05, **P < 0.01 (one-way ANOVA). Error bars depict s.e.m. g Percent survival of p53+/+;Erbb2 and p53+/C;Erbb2 F1 female offspring overexpressing miR-382 in the mammary gland. Twenty-week-old mice (n = 10 per group) were injected in the third mammary gland pairs with lentivirus. P = 0.005 (log-rank). h Whole-mount carmine red stain of the mammary glands from p53+/+;Erbb2 and p53+/C;Erbb2 F1 females injected with lentivirus expressing miR-382. n = 4 mice per group. On the right was the quantification of neoplastic/hyperplastic areas as a percentage of the total gland areas as shown (left) using image analysis. The data were presented as mean + s.e.m. Error bars depict s.e.m. (n = 8 mammary gland from four mice per group) and analyzed with two-sided Student’s t test. i Survival of p53C/C mice overexpressing Pdgfb and an inhibitor to miR-382. Mice were injected in the right SVZ with retrovirus expressing both Pdgfb and anti-miR-382 (n = 9), anti-miR-325 (n = 8), or an inhibitor control (n = 5). P = 0.014 (log-rank test). e, f Source data from Western blotting are provided in a Source Data file
