Hypoxia-Induced FUS-circTBC1D14 Stress Granules Promote Autophagy in TNBC.
Hypoxia-Induced FUS-circTBC1D14 Stress Granules Promote Autophagy in TNBC.
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DOI：
10.1002/advs.202204988
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发表时间：
2023-04
期刊：
影响因子：
15.1
通讯作者：
Yang, Qifeng
中科院分区：
文献类型：
--
作者：
Liu, Ying;Liu, Yiwei;He, Yinqiao;Zhang, Ning;Zhang, Siyue;Li, Yaming;Wang, Xiaolong;Liang, Yiran;Chen, Xi;Zhao, Weijing;Chen, Bing;Wang, Lijuan;Luo, Dan;Yang, Qifeng
三阴性乳腺癌（TNBC）是一种高度侵袭性的乳腺癌亚型，被认为与缺氧有关。这项研究首次发现了一种新的环状RNA (circRNA), circTBC1D14，其表达在TNBC中显著上调。作者证实，circTBC1D14高表达与乳腺癌患者预后不良相关。circTBC1D14相关的质谱和RNA结合蛋白相关的生物信息学策略表明，FUS可以与circTBC1D14相互作用，后者可以结合到circTBC1D14的下游侧边序列诱导环化。FUS是与应激颗粒（SGs）相关的重要生物标志物，作者发现缺氧条件可以在PRMT1蛋白修饰后诱导细胞质中FUS - circtbc1d14相关的SG形成。随后，circTBC1D14通过抑制其K48调控的多泛素化，增加PRMT1的稳定性，导致PRMT1表达上调。此外，FUS-circTBC1D14 SGs可以通过募集LAMP1和增强溶酶体相关的自噬通量，启动SG连接蛋白级联来识别和控制SGs的消除，从而有助于维持细胞稳态并促进TNBC的肿瘤进展。总之，这些发现表明circTBC1D14是一个潜在的预后指标，可以作为TNBC治疗的治疗靶点。FUS‐circTBC1D14‐相关的应激颗粒（SGs）被PRMT1修饰后转移到细胞质中，circTBC1D14通过抑制其K48‐调节的多泛素化而增加了PRMT1的稳定性。然后FUS - circTBC1D14可以启动一系列SGs连接蛋白，通过招募LAMP1来控制SGs的消除。研究结果表明，circTBC1D14可以作为TNBC治疗的治疗靶点。
Triple‐negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is suggested to be associated with hypoxia. This study is the first to identify a novel circular RNA (circRNA), circTBC1D14, whose expression is significantly upregulated in TNBC. The authors confirm that high circTBC1D14 expression is associated with a poor prognosis in patients with breast cancer. circTBC1D14‐associated mass spectrometry and RNA‐binding protein‐related bioinformatics strategies indicate that FUS can interact with circTBC1D14, which can bind to the downstream flanking sequence of circTBC1D14 to induce cyclization. FUS is an essential biomarker associated with stress granules (SGs), and the authors find that hypoxic conditions can induce FUS–circTBC1D14‐associated SG formation in the cytoplasm after modification by protein PRMT1. Subsequently, circTBC1D14 increases the stability of PRMT1 by inhibiting its K48‐regulated polyubiquitination, leading to the upregulation of PRMT1 expression. In addition, FUS–circTBC1D14 SGs can initiate a cascade of SG‐linked proteins to recognize and control the elimination of SGs by recruiting LAMP1 and enhancing lysosome‐associated autophagy flux, thus contributing to the maintenance of cellular homeostasis and promoting tumor progression in TNBC. Overall, these findings reveal that circTBC1D14 is a potential prognostic indicator that can serve as a therapeutic target for TNBC treatment. FUS‐circTBC1D14‐associated stress granules (SGs) are transferred to the cytoplasm after being modified by PRMT1 and circTBC1D14 increases the stability of PRMT1 by inhibiting its K48‐regulated polyubiquitination. Then FUS‐circTBC1D14 can initiate a cascade of SGs‐linked proteins to control the elimination of SGs by recruiting LAMP1. The findings reveal that circTBC1D14 can serve as a therapeutic target for TNBC treatment.
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DOI：
10.1016/j.omtn.2021.09.013
发表时间：
2021-12-03
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Cai Y;Zhao X;Chen D;Zhang F;Chen Q;Shao CC;Ouyang YX;Feng J;Cui L;Chen M;Xu J
通讯作者：
Xu J
影响因子：
9.2
作者：
Fu B;Liu W;Zhu C;Li P;Wang L;Pan L;Li K;Cai P;Meng M;Wang Y;Zhang A;Tang W;An M
通讯作者：
An M
影响因子：
14
作者：
Chung, Chu-Hung;Lu, Kun-Ying;Mi, Fwu-Long
通讯作者：
Mi, Fwu-Long
SQSTM1/p62的氧化介导了氧化还原状态与蛋白质稳态之间的联系。
影响因子：
16.6
作者：
Carroll B;Otten EG;Manni D;Stefanatos R;Menzies FM;Smith GR;Jurk D;Kenneth N;Wilkinson S;Passos JF;Attems J;Veal EA;Teyssou E;Seilhean D;Millecamps S;Eskelinen EL;Bronowska AK;Rubinsztein DC;Sanz A;Korolchuk VI
通讯作者：
Korolchuk VI
C9ORF72和P62的复合物使用精氨酸甲基化来消除自噬的应激颗粒。
影响因子：
16.6
作者：
Chitiprolu M;Jagow C;Tremblay V;Bondy-Chorney E;Paris G;Savard A;Palidwor G;Barry FA;Zinman L;Keith J;Rogaeva E;Robertson J;Lavallée-Adam M;Woulfe J;Couture JF;Côté J;Gibbings D
通讯作者：
Gibbings D