Loss of FTSJ3 promotes R-loop-associated DNA damage and facilitates chemosensitivity in lung cancer cells

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2025-06-13 DOI:10.1016/j.canlet.2025.217877

Hongchengcheng Chen , Guihui Yu , Haodong Lin , Xiao Albert Zhou , Jiansong Liu , Haoyun Liu , Yefei Luo , Kaiqi Cheng , Zuchao Mao , Yujie Ma , Jun Wang , Kezhong Chen , Jiadong Wang , Yun Li

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引用次数: 0

Abstract

R-loop accumulation has emerged as a critical factor that induces DNA damage and compromises genomic integrity. However, the regulatory mechanisms governing the R-loop-induced DNA damage remain unclear. Here, FTSJ3 was determined to be a pivotal regulator of R-loop homeostasis and genomic stability. We demonstrated that FTSJ3 was specifically recruited to R-loop structures, where it prevented DNA damage by suppressing excessive R-loop formation. FTSJ3 expression was significantly upregulated in multiple cancer types, and its elevated expression levels correlated with unfavorable survival in patients with lung adenocarcinoma (LUAD). FTSJ3 depletion increased R-loop-dependent DNA damage. Inhibiting FTSJ3 expression sensitized lung cancer cells to cisplatin both in vitro and in vivo. FTSJ3 could be a genome guardian that limits R-loop-associated damage, suggesting its potential role as a cancer intervention therapeutic target and a predictive biomarker for chemotherapy responsiveness.

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FTSJ3缺失促进r -环相关DNA损伤，促进肺癌细胞的化疗敏感性。

r环积累已成为诱导DNA损伤和损害基因组完整性的关键因素。然而，调控r环诱导的DNA损伤的调控机制尚不清楚。在这里，FTSJ3被确定为R-loop稳态和基因组稳定性的关键调节因子。我们证明了FTSJ3被特异性招募到r环结构中，在那里它通过抑制过量的r环形成来防止DNA损伤。FTSJ3在多种癌症类型中表达显著上调，其表达水平升高与肺腺癌（LUAD）患者的不利生存相关。FTSJ3缺失增加r -环依赖性DNA损伤。体外和体内抑制FTSJ3表达可使肺癌细胞对顺铂致敏。FTSJ3可能是一种限制r -环相关损伤的基因组守护者，表明其作为癌症干预治疗靶点和化疗反应性的预测性生物标志物的潜在作用。

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

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.