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揭示铁死亡相关外泌体非编码 RNA 在癌症发病机制中的作用。

Unveiling the role of ferroptosis-associated exosomal non-coding RNAs in cancer pathogenesis.

机构信息

School of Life Sciences, Fudan University, Shanghai 200438, China; Wanchuanhui (Shanghai) Medical Technology Co., Ltd, Shanghai 201501, China.

出版信息

Biomed Pharmacother. 2024 Mar;172:116235. doi: 10.1016/j.biopha.2024.116235. Epub 2024 Feb 3.

DOI:10.1016/j.biopha.2024.116235
PMID:38308967
Abstract

The pivotal regulatory role of non-coding RNAs (ncRNAs), especially exosomal ncRNAs, in ferroptosis significantly influences cancer cell fate. This review explores their involvement across various human cancers, focusing on microRNAs (miRNA), long non-coding RNAs (lncRNA), and circular RNAs (circRNA). These ncRNAs either stimulate or inhibit ferroptosis by targeting key components, impacting cancer susceptibility to this form of cell death. Specific studies in lung, gastric, liver, cervical, bladder, pancreatic, and osteosarcoma cancers underscore the crucial role of exosomal ncRNAs in modulating ferroptosis, influencing cancer progression, and therapeutic responses. Emphasizing the therapeutic potential of exosomal ncRNAs, we discuss their ability to deliver circRNA, miRNA, and lncRNA to target cells. Despite being in early stages with challenges in bioengineering for drug delivery, these studies hold promise for future clinical applications. Noteworthy findings include inhibiting exosome production to overcome ferroptosis resistance in lung adenocarcinoma and the potential of exosomal DACT3-AS1 to sensitize gastric cancer cells to ferroptosis. The review concludes by highlighting exosomal ncRNAs like miR-4443 and miR-660-5p as promising therapeutic targets, offering avenues for precise cancer interventions by modulating signaling pathways and sensitizing cells to ferroptosis. Overall, this review enhances our understanding of cancer pathogenesis and presents new horizons for targeted therapeutic interventions, revealing the intricate interplay between exosomal ncRNAs and ferroptosis.

摘要

非编码 RNA(ncRNA),尤其是外泌体 ncRNA,在铁死亡中的关键调节作用显著影响癌细胞的命运。本综述探讨了它们在各种人类癌症中的作用,重点关注 microRNA(miRNA)、长链非编码 RNA(lncRNA)和环状 RNA(circRNA)。这些 ncRNA 通过靶向关键成分,刺激或抑制铁死亡,影响癌症对这种细胞死亡形式的易感性。在肺癌、胃癌、肝癌、宫颈癌、膀胱癌、胰腺癌和骨肉瘤中进行的具体研究强调了外泌体 ncRNA 在调节铁死亡、影响癌症进展和治疗反应方面的重要作用。强调外泌体 ncRNA 的治疗潜力,我们讨论了它们将 circRNA、miRNA 和 lncRNA 递送到靶细胞的能力。尽管在生物工程方面存在挑战,用于药物递送,但这些研究为未来的临床应用提供了希望。值得注意的发现包括抑制外泌体的产生,以克服肺腺癌中的铁死亡耐药性,以及外泌体 DACT3-AS1 使胃癌细胞对铁死亡敏感的潜力。该综述最后强调了外泌体 ncRNA 如 miR-4443 和 miR-660-5p 作为有前途的治疗靶点,通过调节信号通路和使细胞对铁死亡敏感,为精确的癌症干预提供了途径。总的来说,本综述增强了我们对癌症发病机制的理解,并为靶向治疗干预提供了新的视角,揭示了外泌体 ncRNA 和铁死亡之间的复杂相互作用。

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