Frontiers in Oncology (Aug 2020)
MicroRNA-221/222 Inhibits the Radiation-Induced Invasiveness and Promotes the Radiosensitivity of Malignant Meningioma Cells
- Qing Zhang,
- Lai-Rong Song,
- Lai-Rong Song,
- Lai-Rong Song,
- Lai-Rong Song,
- Xu-Lei Huo,
- Xu-Lei Huo,
- Xu-Lei Huo,
- Xu-Lei Huo,
- Liang Wang,
- Liang Wang,
- Liang Wang,
- Liang Wang,
- Guo-Bin Zhang,
- Guo-Bin Zhang,
- Guo-Bin Zhang,
- Guo-Bin Zhang,
- Shu-Yu Hao,
- Shu-Yu Hao,
- Shu-Yu Hao,
- Shu-Yu Hao,
- Hai-Wei Jia,
- Chui-Lin Kong,
- Wang Jia,
- Wang Jia,
- Wang Jia,
- Wang Jia,
- Zhen Wu,
- Zhen Wu,
- Zhen Wu,
- Zhen Wu,
- Bai-Nan Xu,
- Gui-Jun Jia,
- Gui-Jun Jia,
- Gui-Jun Jia,
- Gui-Jun Jia,
- Jun-Ting Zhang,
- Jun-Ting Zhang,
- Jun-Ting Zhang,
- Jun-Ting Zhang
Affiliations
- Qing Zhang
- Department of Neurosurgery, Chinese People's Liberation Army General Hospital, Beijing, China
- Lai-Rong Song
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
- Lai-Rong Song
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Lai-Rong Song
- Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
- Lai-Rong Song
- Beijing Key Laboratory of Brain Tumor, Beijing, China
- Xu-Lei Huo
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
- Xu-Lei Huo
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Xu-Lei Huo
- Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
- Xu-Lei Huo
- Beijing Key Laboratory of Brain Tumor, Beijing, China
- Liang Wang
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
- Liang Wang
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Liang Wang
- Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
- Liang Wang
- Beijing Key Laboratory of Brain Tumor, Beijing, China
- Guo-Bin Zhang
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
- Guo-Bin Zhang
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Guo-Bin Zhang
- Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
- Guo-Bin Zhang
- Beijing Key Laboratory of Brain Tumor, Beijing, China
- Shu-Yu Hao
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
- Shu-Yu Hao
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Shu-Yu Hao
- Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
- Shu-Yu Hao
- Beijing Key Laboratory of Brain Tumor, Beijing, China
- Hai-Wei Jia
- Department of Radiotherapy, Beijing Fengtai You Anmen Hospital, Beijing, China
- Chui-Lin Kong
- Department of Radiotherapy, Beijing Fengtai You Anmen Hospital, Beijing, China
- Wang Jia
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
- Wang Jia
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Wang Jia
- Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
- Wang Jia
- Beijing Key Laboratory of Brain Tumor, Beijing, China
- Zhen Wu
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
- Zhen Wu
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Zhen Wu
- Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
- Zhen Wu
- Beijing Key Laboratory of Brain Tumor, Beijing, China
- Bai-Nan Xu
- Department of Neurosurgery, Chinese People's Liberation Army General Hospital, Beijing, China
- Gui-Jun Jia
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
- Gui-Jun Jia
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Gui-Jun Jia
- Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
- Gui-Jun Jia
- Beijing Key Laboratory of Brain Tumor, Beijing, China
- Jun-Ting Zhang
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
- Jun-Ting Zhang
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Jun-Ting Zhang
- Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
- Jun-Ting Zhang
- Beijing Key Laboratory of Brain Tumor, Beijing, China
- DOI
- https://doi.org/10.3389/fonc.2020.01441
- Journal volume & issue
-
Vol. 10
Abstract
The controversy of adjuvant radiotherapy of meningiomas is at least partially due to the insufficient understanding on meningioma cells' response to irradiation and the shortage of radiosensitivity-promotion methods. MicroRNA-221 and microRNA-222 were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in meningiomas has yet to be confirmed. Therefore, the malignant meningioma IOMM-Lee cells were adopted, transfected with microRNA-221/222 mimics or inhibitors, and irradiated with different dosages. The effects of radiation and microRNA-221/222 were then assessed in vitro and in vivo. Radiation dose increases and microRNA-221/222 downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression, and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the microRNA-221/222 expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee's radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for malignant meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the microRNA-221/222 level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.
Keywords
- invasiveness
- radiosensitivity
- microRNA-221/222
- IOMM-Lee
- dose rate
- epithelial–mesenchymal transition-inducing transcription factors
