title: Period2 downregulation inhibits glioma cell apoptosis by activating the MDM2-TP53 pathway.
abstract: The Period2 (Per2) gene is an essential component of the mammalian circadian clock and is strongly linked to glioma occurrence and its response to radiotherapy. Here, we examined the role of Per2 in the response to X-ray-induced DNA damage in U343 glioma cells and in a mouse cancer model. Following low dose X-ray irradiation, we observed that lowering Per2 expression using RNAi reduces DNA damage and cell death in U343 cells and glioma tissue. Additionally, Per2 was associated with increased TP53 activity and was involved in the DNA damage during TP53-mediated apoptosis. These findings suggest that Per2, a core circadian gene, is not only a tumor suppressor gene but can also be regarded as an upstream regulator of TP53. It thus appears that Per2 is an important inhibitor of tumor growth that acts by increasing TP53 expression, DNA damage repair, and apoptosis.
authors.affiliation: Department of Neurosurgery, The General Hospital of Ningxia Medical University, Yinchuan, 750004, China.|Incubation Base of National Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Niu
authors.initials: N
authors.lastname: Zhanfeng
authors.affiliation: The People's Hospital of Liaocheng City, Liaocheng, 252000, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Chengquan
authors.affiliation: Department of Neurosurgery, The General Hospital of Ningxia Medical University, Yinchuan, 750004, China.|Incubation Base of National Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Hechun
authors.affiliation: Ningxia Medical University, Yinchuan, 750004, China.|Incubation Base of National Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Jun
authors.affiliation: Ningxia Medical University, Yinchuan, 750004, China.|Incubation Base of National Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lijian
authors.affiliation: Ningxia Medical University, Yinchuan, 750004, China.|Incubation Base of National Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Ma
authors.initials: M
authors.lastname: Dede
authors.affiliation: Ningxia Medical University, Yinchuan, 750004, China.|Incubation Base of National Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Wenbin
authors.affiliation: Department of ICU, The General Hospital of Ningxia Medical University, Yinchuan, 750004, China.|Incubation Base of National Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Lei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D015536:Down-Regulation; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014965:X-Rays
chemical_list: C421902:PER2 protein, human; D056950:Period Circadian Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: TP53; U343 cells; X-ray; glioma; period2