CCT2 inhibition destabilizes c-Myc and impairs both its transcriptional activity and cisplatin resistance capacity (IMAGE)

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CCT2 inhibition destabilizes c-Myc and impairs both its transcriptional activity and cisplatin resistance capacity

Caption

(A) GSEA analysis of the TCGA HNSCC cohort shows significant enrichment of the MYC Target_V1 pathway in patients with high CCT2 expression. (B) Hallmark enrichment analysis of identified interaction proteins with CCT2 in the BioGRID Database. (C) Network plot of cell cycle-related pathways enriched in CCT2-interacting proteins, with genes representing each pathway. (D) The expression level of c-Myc protein decreased due to CCT2 knockdown in HSC-3 and SAS cells. (E, F) The interaction between CCT2 and c-Myc was tested with co-immunoprecipitation in HSC-3 cells. (G, H) Time-course analysis of c-Myc expression in SAS and HSC-3 cells with or without CCT2 depletion. Cells were treated with cycloheximide (100 μg/mL) for varying periods. (I) Heatmap of cell cycle-related gene expression in the TCGA HNSCC cohort, ordered by CCT2 expression from low to high. (J) Quantitative PCR analysis of the mRNA expression of CCND1, CCNE1, and CDKN1A in HSC-3 cells. (K) Western blotting analysis of c-Myc protein levels in SAS and HSC-3 cells after transfection with c-Myc-targeting shRNA. (L) CCK8 assay was used to assess the sensitivity to cisplatin after c-Myc silencing in SAS and HSC-3 cell lines treated with different concentrations of cisplatin. (M) Apoptosis rate of SAS and HSC-3 cell lines with or without c-Myc knockdown, treated with 10 μM or 20 μM cisplatin for 24 h. Data were presented as mean ± standard deviation. ∗∗p < 0.01 and ∗∗∗p < 0.001 for student's t-test and one-way ANOVA test. CCT2, chaperonin containing TCP1 subunit 2; HNSCC, head and neck squamous cell carcinoma; CCND1, cyclin D1; CCNE1, cyclin E1; CDKN1A, cyclin-dependent kinase inhibitor 1A.

Credit

Lin Lu, Yi Shen, Xuerong Li, Yiwei Zhao, Xuefan Zhai, Min Cai, Baicheng Bao, Guiqing Liao, Jianbo Sun

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