胶质瘤
细胞周期
细胞生长
下调和上调
细胞凋亡
基因敲除
癌症研究
生物
流式细胞术
甲基转移酶
细胞周期检查点
细胞
免疫印迹
细胞培养
分子生物学
化学
甲基化
生物化学
基因
遗传学
作者
Shangfeng Gao,Jiacheng Zhou,Zhiyuan Hu,Shicheng Zhang,Yue Wu,Preethi Priyanka Musunuru,Tong Zhang,Liquan Yang,Xiang Liu,Jing Bai,Qingming Meng,Rutong Yu
标识
DOI:10.1016/j.bbadis.2022.166498
摘要
Previous studies have suggested an important role for N6-methyladenosine (m6A) modification in the proliferation of glioma cells. N6, 2'-O-dimethyladenosine (m6Am) is another methylated form affecting the fate and function of most RNA. PCIF1 has recently been identified as the sole m6Am methyltransferase in mammalian mRNA. However, it remains unknown about the role of PCIF1 in the growth and survival of glioma cells.We constructed glioma cell lines that stably downregulated/upregulated PCIF1, established intracranial xenograft models using these cell lines, and employed the following methods for investigations: CCK-8, EdU, colony formation, flow cytometry, qRT-PCR, Western blot, and immunohistochemistry.Downregulating PCIF1 promoted glioma cell proliferation, while overexpressing PCIF1 showed the opposite effects. Overexpression of PCIF1 blocked cell cycle progression and induced apoptosis in glioma cells, which was further confirmed by alterations in the expression of cell checkpoint proteins and apoptotic markers. Interestingly, disruption of PCIF1 methyltransferase activity slightly reversed the effect of PCIF1 overexpression on cell proliferation, but had no significant reversal effects on cell cycle progression or apoptosis. Knockdown of PCIF1 promoted the growth of gliomas, while overexpressing PCIF1 inhibited tumor growth and prolonged the survival time of tumor-bearing mice. In addition, the mRNA and protein levels of PCIF1 were gradually decreased with the increase of WHO grade in glioma tissues, but there was no significant correlation with patient survival.These results indicated that PCIF1 played a suppressing role in glioma growth and survival, which may not entirely depend on its methyltransferase activity.
科研通智能强力驱动
Strongly Powered by AbleSci AI