首页|LncFASA promotes cancer ferroptosis via modulating PRDX1 phase separation

LncFASA promotes cancer ferroptosis via modulating PRDX1 phase separation

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Ferroptosis,a unique type of non-apoptotic cell death resulting from iron-dependent lipid peroxidation,has a potential physiological function in tumor suppression,but its underlying mechanisms have not been fully elucidated.Here,we report that the long non-coding RNA(lncRNA)LncFASA increases the susceptibility of triple-negative breast cancer(TNBC)to ferroptosis.As a tumor suppressor,LncFASA drives the formation of droplets containing peroxiredoxinl(PRDX1),a member of the peroxidase family,resulting in the accumulation of lipid peroxidation via the SLC7A11-GPX4 axis.Mechanistically,LncFASA directly binds to the Ahpc-TSA domain of PRDX1,inhibiting its per-oxidase activity by driving liquid-liquid phase separation,which disrupts intracellular ROS homeostasis.Notably,high LncFASA expression indicates favorable overall survival in individuals with breast cancer,and LncFASA impairs the growth of breast xenograft tumors by modulating ferroptosis.Together,our findings illustrate the crucial role of this lncRNA in ferroptosis-mediated cancer development and provide new insights into therapeutic strategies for breast cancer.

long non-coding RNAperoxiredoxinliquid-liquid phase separationferroptosisbreast cancer

Xiao Fan、Fangzhou Liu、Xiang Wang、Ying Wang、Yu Chen、Chengyu Shi、Xinwan Su、Manman Tan、Qingfeng Yan、Jinrong Peng、Jianzhong Shao、Yan Xiong、Aifu Lin

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MOE Laboratory of Biosystem Homeostasis and Protection,College of Life Sciences,Zhejiang University,Hangzhou 310058,China

Key Laboratory of Cancer Prevention and Intervention,China National Ministry of Education,Hangzhou 310009,China

Cancer Center,Zhejiang University,Hangzhou 310058,China

Key Laboratory for Cell and Gene Engineering of Zhejiang Province,Hangzhou 310058,China

Department of Central Laboratory,the First People's Hospital of Huzhou,Huzhou 313000,China

Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Hangzhou 310006,China

MOE Key Laboratory for Molecular Animal Nutrition,College of Animal Sciences,Zhejiang University,Hangzhou 310058,China

Department of Orthopedic Surgery,the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310000,China

Breast Center of the First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310003,China

International School of Me

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国家杰出青年科学基金国家重点研发计划国家自然科学基金国家自然科学基金国家自然科学基金Zhejiang Provincial Natural Science Fund for Distinguished Young Scholars of China"Lingyan"Research and Development Research and Development Project

322250142021YFC2700903816727918187230082071567LR18C0600022023C03023

2024

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子:0.806
ISSN:1674-7305
年,卷(期):2024.67(3)
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