Ionizing radiation-induced long noncoding RNA CRYBG3 regulates YAP/TAZ through mechanotransduction
Lijun Zheng1, Chenyu Luo1, Nan Yang1
1State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou, China.
Abstract:
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.
Insights
Long noncoding RNA CRYBG3 inhibits lung cancer progression by disrupting mechanotransduction pathways. This radiotherapy mediator blunts YAP/TAZ activity, reducing tumor growth, invasion, and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biophysics
Background:
- Cellular mechanotransduction and long noncoding RNAs (lncRNAs) are crucial in cancer development and treatment.
- The interplay between lncRNAs and cancer mechanotransduction remains largely unexplored.
Purpose of the Study:
- To investigate the role of lncRNAs in cancer mechanotransduction.
- To elucidate the function of lncRNA CRYBG3 in lung cancer progression and response to radiotherapy.
Main Methods:
- Atomic force microscopy (AFM) to assess tumor stiffness.
- Analysis of YAP/TAZ activity and downstream signaling pathways.
- In vivo studies in mouse models of lung cancer.
Main Results:
- Ionizing radiation decreases tumor stiffness.
- lncRNA CRYBG3 inhibits YAP/TAZ activity by interfering with mechanotransduction, reducing proliferation, invasion, and metastasis.
- Loss of CRYBG3 enhances tumor initiation and metastasis, effects abolished by TAZ depletion.
- CRYBG3 dysregulates F-actin organization, activates LATS1/2, leading to YAP/TAZ nuclear exclusion.
Conclusions:
- lncRNA CRYBG3 acts as a radiotherapy mediator by controlling cancer-tissue mechanotransduction.
- CRYBG3 regulates YAP/TAZ activity, impacting tumor growth and metastasis in lung cancer.
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