Cheng Y, Zhu Y, Xiao M, Zhang Y, Wang Z, Chen H, Cao K

Circular RNAs (circRNAs) play important roles in tumour progression. This study aimed to explore the mechanism of hsa_circ_0067717 (termed circRNA_0067717) promoting paclitaxel resistance in nasopharyngeal carcinoma (NPC).We assayed CNE-1 and HNE-2 parental cell lines and the corresponding paclitaxel-resistant NPC cell lines using circRNA microarrays. RNA pull-down assay, RNA immunoprecipitation, and ...

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RNA fluorescence in situ hybridization were used to identify the molecular mechanisms.Here, we confirm that circRNA_0067717 is significantly upregulated in NPC paclitaxel-resistant cells and is associated with paclitaxel resistance in NPC. Mechanistically, circRNA_0067717 functions as a scaffold for TRIM41 protein (a ubiquitin E3 ligase) and p53 protein. In nasopharyngeal carcinoma paclitaxel-resistant cells, the highly expressed circRNA_0067717 can bind to more TRIM41 and p53 protein, promoting TRIM41-induced p53 ubiquitination and degradation, resulting in a decrease in p53 protein level. Moreover, the 1-176 nt area of circRNA_0067717 and the 301-425 nt region of circRNA_0067717 are the binding sites for p53 and TRIM41, respectively. The resistance of NPC cells to paclitaxel can be reduced by blocking these binding regions of circRNA_0067717.We demonstrate that circRNA_0067717 acts as a scaffold for TRIM41 and p53, enhancing paclitaxel chemoresistance in NPC by promoting TRIM41-induced p53 degradation via ubiquitination.

Date: Jun. 01, 2023

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