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. Author manuscript; available in PMC: 2018 Sep 15.
Published in final edited form as: Cancer Res. 2017 Jul 7;77(18):5011–5025. doi: 10.1158/0008-5472.CAN-16-2704

Figure 6. HuR silencing in vivo enhances olaparib- mediated suppression of PDA xenograft growth.

Figure 6

Mia.shHuR xenografts in athymic, nude mice were randomized into DOX and olaparib treatment groups. (A) Tumor volumes are plotted, with each point representing the mean ± 2SE of each group, *P<0.05. Inset shows differences in number of duplications. (B) Representative image of mice and tumor per group. (C) Tumor duplication time (days) per group (D) HuR, PARG and PARP-1 mRNA expression in extracted tumors, relative to vehicle- treated –DOX group. Each bar represents the mean ± SEM (n = 3 per group). (E) HuR protein expression when tumors were harvested (day 36, n=3). (F) Working model: In response to PARPi stress, cytoplasmic HuR binds to and stabilizes PARG mRNA, thereby increasing PARG expression and modulating PARP1-chromatin dynamics. HuR and PARG inhibition breaks such acute resistance by enhancing chromatin- trapped PARP-1 and accumulation of damaged DNA and apoptosis.