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环状RNA:膀胱癌化疗耐药和免疫逃逸背后的驱动力

Circular RNAs: driving forces behind chemoresistance and immune evasion in bladder cancer.

作者信息

Saadh Mohamed J, Hussein Wael Sheet, Al-Hussainy Ali Fawzi, Bishoyi Ashok Kumar, Rekha M M, Kundlas Mayank, Kavitha V, Aminov Zafar, Taher Sada Ghalib, Alwan Mariem, Jawad Mahmood, Mushtaq Hiba

机构信息

Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan.

Dental Prosthetics Techniques Department, Health and Medical Techniques College, Alnoor University, Mosul, Iraq.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar 25. doi: 10.1007/s00210-025-04032-y.

Abstract

Bladder cancer (BCa) is characterized by recurring relapses and the emergence of chemoresistance, especially against standard treatments like cisplatin and gemcitabine. Despite its significance, the molecular mechanisms underlying chemoresistance in BCa remain elusive. Recent studies have revealed that circular RNAs (circRNAs) are pivotal regulators of cancer progression and chemoresistance. Through their function as miRNA sponges and protein sequesters, circRNAs modulate the expression of key genes, ultimately driving either drug resistance or sensitivity in BCa. The complex interplay between circRNAs and chemoresistance suggests that they may represent promising therapeutic targets for overcoming treatment resistance in patients with BCa. This review aims to summarize the current understanding of circRNAs' regulatory roles in chemoresistance and provide insights into their potential as therapeutic targets, particularly in the context of cisplatin and gemcitabine resistance. Furthermore, we explore how chemoresistance can also impact tumor immune evasion, thereby affecting the tumor microenvironment. Our findings may pave the way for the advancement of innovative treatment approaches for bladder cancer.

摘要

膀胱癌(BCa)的特点是复发频繁且出现化疗耐药,尤其是对顺铂和吉西他滨等标准治疗产生耐药。尽管其具有重要意义,但BCa中化疗耐药的分子机制仍不清楚。最近的研究表明,环状RNA(circRNAs)是癌症进展和化疗耐药的关键调节因子。通过作为微小RNA(miRNA)海绵和蛋白质隔离物的功能,circRNAs调节关键基因的表达,最终导致BCa中的耐药或敏感。circRNAs与化疗耐药之间的复杂相互作用表明,它们可能是克服BCa患者治疗耐药的有前景的治疗靶点。本综述旨在总结目前对circRNAs在化疗耐药中的调节作用的理解,并深入探讨它们作为治疗靶点的潜力,特别是在顺铂和吉西他滨耐药的背景下。此外,我们还探讨了化疗耐药如何影响肿瘤免疫逃逸,从而影响肿瘤微环境。我们的研究结果可能为膀胱癌创新治疗方法的发展铺平道路。

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