Upregulation of Gfi1 induced by LSD1 inhibitor protects against cisplatin-induced ototoxicity through attenuating pyroptosis

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2026-03-15 Epub Date: 2026-01-19 DOI:10.1016/j.yexcr.2026.114902

Zihe Zhao , Jingjing Luo , Dengbin Ma , Siyu Li , Shaoqin Cen , Hanqi Fan , Zhenxing Hou , Junze Lu , Cheng Cheng , Xiaoyun Qian , Xia Gao , Ao Li

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引用次数: 0

Abstract

Cisplatin, a widely used chemotherapeutic agent, is associated with significant ototoxicity. Identifying potential therapeutic targets to mitigate cisplatin-induced hearing loss has become a crucial goal. In this study, we demonstrated that the LSD1 inhibitor S2101 could protect against cisplatin-induced ototoxicity (CIO) by upregulating Gfi1 expression. Mechanistically, we investigated the regulatory relationship between Gfi1 and Trim27. Our findings indicated that Gfi1 could bind to the Trim27 promoter region, activating its transcription. The subsequent upregulation of Trim27 significantly attenuated hair cell pyroptosis, highlighting the therapeutic potential of the Gfi1-Trim27 pathway. These results collectively underscore the critical function of Gfi1 in protecting against cisplatin-induced hearing loss and provide novel insights into potential therapeutic strategies.

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LSD1抑制剂诱导的Gfi1上调通过减轻焦亡保护顺铂诱导的耳毒性

顺铂是一种广泛使用的化疗药物，具有显著的耳毒性。确定潜在的治疗靶点以减轻顺铂引起的听力损失已成为关键目标。在这项研究中，我们证明LSD1抑制剂S2101可以通过上调Gfi1的表达来保护顺铂诱导的耳毒性（CIO）。在机制上，我们研究了Gfi1和Trim27之间的调控关系。我们的研究结果表明，Gfi1可以结合到Trim27启动子区域，激活其转录。随后Trim27的上调显著减轻了毛细胞焦亡，突出了Gfi1-Trim27通路的治疗潜力。这些结果共同强调了Gfi1在预防顺铂性听力损失方面的关键功能，并为潜在的治疗策略提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.