生物
癌变
癌症研究
细胞生物学
癌症
胞浆
细胞凋亡
抑制器
癌细胞
染色质
转录因子
平方毫米
基因
遗传学
生物化学
酶
作者
Chao Mao,Xiang Wang,Yating Liu,Min Wang,Bin Yan,Yiqun Jiang,Ying Shi,Siyan Yi,Xiaoli Liu,Weiwei Lai,Rui Yang,Desheng Xiao,Yan Cheng,Shuang Liu,Hu Zhou,Yang Cao,Weishi Yu,Kathrin Muegge,Herbert Yu,Yongguang Tao
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2018-07-01
卷期号:78 (13): 3484-3496
被引量:351
标识
DOI:10.1158/0008-5472.can-17-3454
摘要
Abstract Long noncoding RNAs (lncRNA) have been associated with various types of cancer; however, the precise role of many lncRNAs in tumorigenesis remains elusive. Here we demonstrate that the cytosolic lncRNA P53RRA is downregulated in cancers and functions as a tumor suppressor by inhibiting cancer progression. Chromatin remodeling proteins LSH and Cfp1 silenced or increased P53RRA expression, respectively. P53RRA bound Ras GTPase-activating protein-binding protein 1 (G3BP1) using nucleotides 1 and 871 of P53RRA and the RRM interaction domain of G3BP1 (aa 177-466). The cytosolic P53RRA–G3BP1 interaction displaced p53 from a G3BP1 complex, resulting in greater p53 retention in the nucleus, which led to cell-cycle arrest, apoptosis, and ferroptosis. P53RRA promoted ferroptosis and apoptosis by affecting transcription of several metabolic genes. Low P53RRA expression significantly correlated with poor survival in patients with breast and lung cancers harboring wild-type p53. These data show that lncRNAs can directly interact with the functional domain of signaling proteins in the cytoplasm, thus regulating p53 modulators to suppress cancer progression. Significance: A cytosolic lncRNA functions as a tumor suppressor by activating the p53 pathway. Cancer Res; 78(13); 3484–96. ©2018 AACR.
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