Research Paper Volume 13, Issue 19 pp 23119—23132

Ribosome profiling reveals translatome remodeling in cancer cells in response to zinc oxide nanoparticles

CCNB1IP1 and TLNRD1 promote ZnO NPs-induced cytotoxicity. (A) Luciferase constructs with wild type (WT) or mutated (Mut) uORF of CCNB1IP1. (B) Luciferase activity of the constructs in (A) with or without ZnO NPs treatment. Data are represented as mean ± SEM. **P n = 3, t-test). (C) Luciferase constructs with wild type (WT) or mutated (Mut) uORF of TLNRD1. (D) Luciferase activity of the constructs in (C) with or without ZnO NPs treatment. Data are represented as mean ± SEM. ***P *P n = 3, t-test). (E) Knockdown efficiency of TLNRD1 and CCNB1IP1 in A549 cells. (F) Cell viability of A549 cells with different treatment. **P n = 5, t-test). (G) Schematic of ZnO NP-induced translatome remodeling in cancer cell survival. ZnO NPs phosphorylate eIF2α through ROS or other mechanisms. eIF2α phosphorylation reduces uORF translation and induces the translational induction of stress-responsive genes including ATF4, ATF5, CCNB1IP1, and TLNRD1.

Figure 5. CCNB1IP1 and TLNRD1 promote ZnO NPs-induced cytotoxicity. (A) Luciferase constructs with wild type (WT) or mutated (Mut) uORF of CCNB1IP1. (B) Luciferase activity of the constructs in (A) with or without ZnO NPs treatment. Data are represented as mean ± SEM. **P < 0.01 (n = 3, t-test). (C) Luciferase constructs with wild type (WT) or mutated (Mut) uORF of TLNRD1. (D) Luciferase activity of the constructs in (C) with or without ZnO NPs treatment. Data are represented as mean ± SEM. ***P < 0.001, *P < 0.05 (n = 3, t-test). (E) Knockdown efficiency of TLNRD1 and CCNB1IP1 in A549 cells. (F) Cell viability of A549 cells with different treatment. **P < 0.01 (n = 5, t-test). (G) Schematic of ZnO NP-induced translatome remodeling in cancer cell survival. ZnO NPs phosphorylate eIF2α through ROS or other mechanisms. eIF2α phosphorylation reduces uORF translation and induces the translational induction of stress-responsive genes including ATF4, ATF5, CCNB1IP1, and TLNRD1.