Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-09 DOI:10.1016/j.celrep.2024.115142

Minjie Fu, Mengli Zhang, Licheng Zhang, Yuan Feng, Chao Gao, Hao Xu, Jinsen Zhang, Huaichao Zhang, Tianping Peng, Youjun Chu, Yonghe Wu, Pu Wang, Dan Ye, Ying Mao, Wei Hua

引用次数: 0

Abstract

Glioblastoma (GBM) is a highly lethal malignant brain tumor with poor survival rates, and chemoresistance poses a significant challenge to the treatment of patients with GBM. Here, we show that transketolase (TKT), a metabolic enzyme in the pentose phosphate pathway (PPP), attenuates the chemotherapy sensitivity of glioma cells in a manner independent of catalytic activity. Mechanistically, chemotherapeutic drugs can facilitate the translocation of TKT protein from the cytosol into the nucleus, where TKT physically interacts with XRN2 to regulate the resolution and removal of R-loops. Depletion of TKT leads to increased R-loop accumulation and genome instability, increasing the susceptibility of glioma cells to chemotherapy. In conclusion, our study reveals a non-metabolic function of TKT in regulating R-loop dynamics, genome instability, and chemotherapy sensitivity in gliomas.

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转酮醇酶通过调节r环的形成来减弱胶质瘤细胞的化疗敏感性。

胶质母细胞瘤（Glioblastoma， GBM）是一种高致死率、生存率低的恶性脑肿瘤，化疗耐药对GBM患者的治疗提出了重大挑战。在这里，我们发现转酮醇酶（TKT），戊糖磷酸途径（PPP）中的一种代谢酶，以一种独立于催化活性的方式减弱胶质瘤细胞的化疗敏感性。从机制上讲，化疗药物可以促进TKT蛋白从细胞质转运到细胞核，在细胞核中，TKT与XRN2物理相互作用以调节r环的分解和去除。TKT的缺失导致r环积累增加和基因组不稳定，增加胶质瘤细胞对化疗的易感性。总之，我们的研究揭示了TKT在调节胶质瘤中r -环动力学、基因组不稳定性和化疗敏感性方面的非代谢功能。

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

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.