circRNA_0067717 promotes paclitaxel resistance in nasopharyngeal carcinoma by acting as a scaffold for TRIM41 and p53

• Published in: Cellular oncology (Dordrecht) Vol. 46; no. 3; pp. 677 - 695
• Main Authors: Cheng, Yaxin, Zhu, Yuxing, Xiao, Mengqing, Zhang, Yeyu, Wang, Zhanwang, Chen, Haotian, Cao, Ke
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.06.2023; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cell Line, Tumor; Cell Proliferation; Chemoresistance; Fluorescence in situ hybridization; Humans; Immunoprecipitation; In Situ Hybridization, Fluorescence; MicroRNAs - genetics; Molecular modelling; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - genetics; Nasopharyngeal Neoplasms - genetics; Oncology; p53 Protein; Paclitaxel; Paclitaxel - pharmacology; Pathology; Proteins; Ribonucleic acid; RNA; RNA, Circular - genetics; Tumor Suppressor Protein p53 - genetics; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligases; Ubiquitination; Nasopharyngeal carcinoma; Chemotherapy resistance; TRIM41; circRNA_0067717; p53
• ISSN: 2211-3428; 2211-3436; 2211-3436
• DOI: 10.1007/s13402-023-00776-y

Purpose 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). Methods 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 RNA fluorescence in situ hybridization were used to identify the molecular mechanisms. Results 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. Conclusion 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.