Статья

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

Chao Mao1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, ChinaXiang WangSecond Xiangya Hospital of Central South UniversityYating Liu1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, ChinaMin Wang1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, ChinaBin Yan1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, ChinaYiqun Jiang1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, ChinaYing Shi1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, ChinaYi Shen4Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HawaiiXiaoli Liu1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, ChinaWeiwei Lai1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, ChinaRui Yang1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, ChinaDesheng Xiao5Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaYan Cheng6Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, ChinaShuang Liu7Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaHu Zhou8Shanghai Institute of Material Medica, Chinese Academy of Sciences (CAS), Zhangjiang Hi-Tech Park, Shanghai, ChinaYa Cao1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, ChinaWeishi Yu9Cipher Gene (Beijing) Co., Ltd., Beijing, ChinaKathrin Muegge10Mouse Cancer Genetics Program, National Cancer Institute, Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MarylandHerbert Yu4Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HawaiiYongguang Tao1Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Hunan, China

2018en

ABI

Аннотация

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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Идентификаторы

DOI: 10.1158/0008-5472.can-17-3454

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar