A G3BP1-Interacting lncRNA Promotes Ferroptosis and Apoptosis in Cancer via Nuclear Sequestration of p53

Release time:2020-07-13

Impact Factor:9.727

Affiliation of Author(s):中南大学

Journal:Cancer Res

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

Co-author:Xiang Wang, Yating Liu, Min Wang, Bin Yan, Yiqun Jiang, Ying Shi, Yi Shen, Xiaoli Liu, Weiwei Lai, Rui Yang, Desheng Xiao, Yan Cheng, Shuang Liu, Hu Zhou, Ya Cao, Weishi Yu, Kathrin Muegge, Herbert Yu

First Author:Chao Mao

Indexed by:Journal paper

Correspondence Author:Yongguang Tao

Volume:78(13)

Page Number:3484-3496

Translation or Not:no

Date of Publication:2018-07-01

Included Journals:SCI