Ionizing radiation-induced long noncoding RNA CRYBG3 regulates YAP/TAZ through mechanotransduction.
Ionizing radiation-induced long noncoding RNA CRYBG3 regulates YAP/TAZ through mechanotransduction.
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DOI：
10.1038/s41419-022-04650-x
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发表时间：
2022-03-04
影响因子：
9
通讯作者：
Chang L
中科院分区：
文献类型：
--
作者：
Zheng L;Luo C;Yang N;Pei H;Ji M;Shu Y;Zhang Z;Dong S;Wang X;Li X;Zhang W;Wang Y;Li B;Hei TK;Zhou G;Chang L
组织结构和细胞微环境的机械转导传感是细胞命运（包括癌症）的基本调节剂。与此同时，长非编码RNA (lncRNA) 在癌症发展和治疗过程中发挥多种功能。然而，lncRNA 与癌症进展背景下的细胞力转导之间的联系尚未阐明。在这项研究中，我们使用原子力显微镜（AFM）发现电离辐射降低了肿瘤硬度。电离辐射诱导的lncRNA CRYBG3可以通过干扰力转导来减弱YAP/TAZ活性，从而抑制肺癌细胞的细胞增殖、侵袭和转移。在体内，我们发现lncRNA CRYBG3的缺失可以增强肿瘤的起始和转移能力，但这被伴随的TAZ耗尽所消除。在分子水平上，lncRNA CRYBG3 反过来会失调 F-肌动蛋白组织，激活 LATS1/2 激酶，所有这些都会导致 YAP/TAZ 核排斥。我们的研究提出，lncRNA CRYBG3 通过控制癌组织机械转导和连接 YAP/TAZ 活性来控制肿瘤生长和转移，从而成为放射治疗的介质。
Mechanotransduction sensing of tissue architecture and cellular microenvironment is a fundamental regulator of cell fate, including cancer. Meanwhile, long noncoding RNAs (lncRNAs) play multifunctions during cancer development and treatment. However, the link between lncRNAs and cellular mechanotransduction in the context of cancer progression has not yet been elucidated. In this study, using atomic force microscopy (AFM), we find that ionizing radiation reduces tumor stiffness. Ionizing radiation-induced lncRNA CRYBG3 can blunt YAP/TAZ activity through interference with mechanotransduction, resulting in the inhibition of cell proliferation, invasion, and metastasis of lung cancer cells. In vivo, we found that loss of lncRNA CRYBG3 could power the tumor initiation and metastasis ability, but this was abolished by concomitant deplete TAZ. At the molecular level, lncRNA CRYBG3 that in turn dysregulates F-actin organization, activates the LATS1/2 kinase, all in all resulting in YAP/TAZ nuclear exclusion. Our research proposes that lncRNA CRYBG3 is a mediator of radiotherapy through its control of cancer-tissue mechanotransduction and wiring YAP/TAZ activity to control tumor growth and metastasis.
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影响因子：
64.8
作者：
Chang L;Azzolin L;Di Biagio D;Zanconato F;Battilana G;Lucon Xiccato R;Aragona M;Giulitti S;Panciera T;Gandin A;Sigismondo G;Krijgsveld J;Fassan M;Brusatin G;Cordenonsi M;Piccolo S
通讯作者：
Piccolo S
影响因子：
4.7
作者：
Gilreath C;Boerma M;Qin Z;Hudson MK;Wang S
通讯作者：
Wang S
影响因子：
4.7
作者：
Lo Sardo, Federica;Forcato, Mattia;Blandino, Giovanni
通讯作者：
Blandino, Giovanni
影响因子：
16
作者：
Andrianantoandro, Ernesto;Pollard, Thomas D.
通讯作者：
Pollard, Thomas D.
影响因子：
25.7
作者：
Pocaterra, Arianna;Santinon, Giulia;Dupont, Sirio
通讯作者：
Dupont, Sirio