Details

Autor(en) / Beteiligte

• Lyu, Fang
• Huang, Sihuai
• Yan, Zhecheng
• He, Qingliu
• Liu, Chunyu
• Cheng, Lulin
• Cong, Yukun
• Chen, Kang
• Song, Yarong
• Xing, Yifei

Titel

CircUGGT2 facilitates progression and cisplatin resistance of bladder cancer through nonhomologous end-joining pathway

Ist Teil von

• Cellular signalling, 2024-07, Vol.119, p.111164-111164, Article 111164

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The development of resistance to cisplatin (CDDP) in bladder cancer presents a notable obstacle, with indications pointing to the substantial role of circular RNAs (circRNAs) in this resistance. Nevertheless, the precise mechanisms through which circRNAs govern resistance are not yet fully understood. Our findings demonstrate that circUGGT2 is significantly upregulated in bladder cancer, facilitating cancer cell migration and invasion. Additionally, our analysis of eighty patient outcomes revealed a negative correlation between circUGGT2 expression levels and prognosis. Using circRNA pull-down assays, mass spectrometry analyses, and RNA Immunoprecipitation (RIP), it was shown that circUGGT2 interacts with the KU heterodimer, consisting of KU70 and KU80. Both KU70 and KU80 are critical components of the non-homologous end joining (NHEJ) pathway, which plays a role in CDDP resistance. Flow cytometry was utilized in this study to illustrate the impact of circUGGT2 on the sensitivity of bladder cancer cell lines to CDDP through its interaction with KU70 and KU80. Additionally, a reduction in the levels of DNA repair factors associated with the NHEJ pathway, such as KU70, KU80, DNA-PKcs, and XRCC4, was observed in chromatin of bladder cancer cells following circUGGT2 knockdown post-CDDP treatment, while the levels of DNA repair factors in total cellular proteins remained constant. Thus, the promotion of CDDP resistance by circUGGT2 is attributed to its facilitation of repair factor recruitment to DNA breaks via interaction with the KU heterodimer. Furthermore, our study demonstrated that knockdown of circUGGT2 resulted in reduced levels of γH2AX, a marker of DNA damage response, in CDDP-treated bladder cancer cells, implicating circUGGT2 in the NHEJ pathway for DNA repair. •CircUGGT2, highly expressed in bladder cancer, significantly promotes its invasion and affects patient prognosis.•CircUGGT2 binds to KU70 and KU80, facilitating the dimerization and thereby enhancing the NHEJ pathway.•CircUGGT2 enhances DNA double-strand repair, thereby enhancing cisplatin resistance in bladder cancer.