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

Frontiers in Oncology

Shu-Yu Hao¹  Guo-Bin Zhang¹  Gui-Jun Jia¹  Xu-Lei Huo¹  Liang Wang¹  Zhen Wu¹  Lai-Rong Song¹  Wang Jia¹  Jun-Ting Zhang¹  Qing Zhang⁵  Bai-Nan Xu⁵  Hai-Wei Jia⁶  Chui-Lin Kong⁶ 

[1] Beijing Key Laboratory of Brain Tumor, Beijing, China;Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China;China National Clinical Research Center for Neurological Diseases, Beijing, China;Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China;Department of Neurosurgery, Chinese People's Liberation Army General Hospital, Beijing, China;Department of Radiotherapy, Beijing Fengtai You Anmen Hospital, Beijing, China;

关键词: invasiveness;    radiosensitivity;    microRNA-221/222;    IOMM-Lee;    dose rate;    epithelial–mesenchymal transition-inducing transcription factors;   

DOI  :  10.3389/fonc.2020.01441

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown