| Literature DB >> 29588351 |
Chao Mao1,2, Xiang Wang3, Yating Liu1,2, Min Wang1,2, Bin Yan1,2, Yiqun Jiang1,2,3, Ying Shi1,2, Yi Shen4, Xiaoli Liu1,2, Weiwei Lai1,2, Rui Yang1,2, Desheng Xiao5, Yan Cheng6, Shuang Liu7, Hu Zhou8, Ya Cao1,2, Weishi Yu9, Kathrin Muegge10, Herbert Yu4, Yongguang Tao11,2,3.
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. ©2018 American Association for Cancer Research.Entities:
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Year: 2018 PMID： 29588351 PMCID： PMC8073197 DOI： 10.1158/0008-5472.CAN-17-3454
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701