MicroRNA-221/222 Inhibits the Radiation-Induced Invasiveness and Promotes the Radiosensitivity of Malignant Meningioma Cells.

Autor:	Zhang Q; Department of Neurosurgery, Chinese People's Liberation Army General Hospital, Beijing, China., Song LR; Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Brain Tumor, Beijing, China., Huo XL; Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Brain Tumor, Beijing, China., Wang L; Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Brain Tumor, Beijing, China., Zhang GB; Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Brain Tumor, Beijing, China., Hao SY; Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Brain Tumor, Beijing, China., Jia HW; Department of Radiotherapy, Beijing Fengtai You Anmen Hospital, Beijing, China., Kong CL; Department of Radiotherapy, Beijing Fengtai You Anmen Hospital, Beijing, China., Jia W; Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Brain Tumor, Beijing, China., Wu Z; Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Brain Tumor, Beijing, China., Xu BN; Department of Neurosurgery, Chinese People's Liberation Army General Hospital, Beijing, China., Jia GJ; Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Brain Tumor, Beijing, China., Zhang JT; Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Brain Tumor, Beijing, China.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2020 Aug 25; Vol. 10, pp. 1441. Date of Electronic Publication: 2020 Aug 25 (Print Publication: 2020).
DOI:	10.3389/fonc.2020.01441
Abstrakt:	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. (Copyright © 2020 Zhang, Song, Huo, Wang, Zhang, Hao, Jia, Kong, Jia, Wu, Xu, Jia and Zhang.)
Databáze:	MEDLINE
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