A tumor-suppressive circular RNA mediates uncanonical integrin degradation by the proteasome in liver cancer.
A tumor-suppressive circular RNA mediates uncanonical integrin degradation by the proteasome in liver cancer.
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抑制肿瘤的环状RNA介导肝癌中蛋白酶体对非典型整合素的降解
DOI：
10.1126/sciadv.abe5043
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发表时间：
2021-03
期刊：
影响因子：
13.6
通讯作者：
Cai X
中科院分区：
文献类型：
--
作者：
Shi L;Liu B;Shen DD;Yan P;Zhang Y;Tian Y;Hou L;Jiang G;Zhu Y;Liang Y;Liang X;Shen B;Yu H;Zhang Y;Wang Y;Guo X;Cai X
一种肿瘤抑制性环状RNA引入蛋白酶体，摧毁肝癌细胞的立足点。环状RNA（circRNA）已成为各种细胞过程的重要调节因子，并与癌症有关。以前，我们报道了在人肝细胞癌（HCC）中发现了几种失调的circRNA，包括circPABPC1（多聚腺苷酸结合蛋白1），尽管它们在HCC发展中的作用尚不清楚。在这里，我们发现circPABPC 1优先在临床样本的肿瘤细胞中丢失，并在小鼠异种移植模型中抑制肝内和远处转移。circPABPC 1的这种肿瘤抑制功能可归因于其通过下调整联蛋白家族的关键成员ITGB 1（β1整联蛋白）来抑制细胞粘附和迁移。质谱和生化证据表明，circPABPC 1直接连接ITGB 1的26 S蛋白酶体降解的泛素化不依赖的方式。我们的数据揭示了整合素周转的非经典途径和HCC中circRNA先前未识别的作用模式，可用于抗癌治疗。
A tumor-suppressive circular RNA brings in the proteasome to destroy the foothold of liver cancer cells. Circular RNAs (circRNAs) have emerged as important regulators of various cellular processes and have been implicated in cancer. Previously, we reported the discovery of several dysregulated circRNAs including circPABPC1 (polyadenylate-binding protein 1) in human hepatocellular carcinoma (HCC), although their roles in HCC development remained unclear. Here, we show that circPABPC1 is preferentially lost in tumor cells from clinical samples and inhibits both intrahepatic and distant metastases in a mouse xenograft model. This tumor-suppressive function of circPABPC1 can be attributed to its inhibition of cell adhesion and migration through down-regulating a key member of the integrin family, ITGB1 (β1 integrin). Mass spectrometry and biochemical evidence demonstrate that circPABPC1 directly links ITGB1 to the 26S proteasome for degradation in a ubiquitination-independent manner. Our data have revealed an uncanonical route for integrin turnover and a previously unidentified mode of action for circRNAs in HCC that can be harnessed for anticancer treatment.
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位点特异性蛋白酶体磷酸化控制细胞增殖和肿瘤发生。
影响因子：
21.3
作者：
Guo X;Wang X;Wang Z;Banerjee S;Yang J;Huang L;Dixon JE
通讯作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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