机构：[1]Department of Hematology, Affiliated Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministr y of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China[3]Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA[4]Department of General Practice, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Multiple myeloma is a malignant plasma-cell disease, which is highly dependent on the hypoxic bone marrow microenvironment. However, the underlying mechanisms of hypoxia contributing to myeloma genesis are not fully understood. Here, we show that long non-coding RNA DARS-AS1 in myeloma is directly upregulated by hypoxia inducible factor (HIF)-1. Importantly, DARS-AS1 is required for the survival and tumorigenesis of myeloma cells both in vitro and in vivo. DARS-AS1 exerts its function by binding RNA-binding motif protein 39 (RBM39), which impedes the interaction between RBM39 and its E3 ubiquitin ligase RNF147, and prevents RBM39 from degradation. The overexpression of RBM39 observed in myeloma cells is associated with poor prognosis. Furthermore, knockdown of DARS-AS1 inhibits the mammalian target of rapamycin signaling pathway, an effect that is reversed by RBM39 overexpression. We reveal that a novel HIF-1/DARS-AS1/RBM39 pathway is implicated in the pathogenesis of myeloma. Targeting DABS-AS1/RBM39 may, therefore, represent a novel strategy to combat myeloma.
基金：
National
Key Research and Development Program of China (n.
2017YFA0505200), National Natural Science Foundation of
China (8167010684, 81570118), Shanghai Commission of
Science and Technology (16ZR1421400), and the Science and
Technology Committee of Shanghai (15401901800).
第一作者机构：[1]Department of Hematology, Affiliated Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Hematology, Affiliated Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China[4]Department of General Practice, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
推荐引用方式(GB/T 7714)：
Tong Jia,Xu Xiaoguang,Zhang Zilu,et al.Hypoxia-induced long non-coding RNA DARS-AS1 regulates RBM39 stability to promote myeloma malignancy[J].HAEMATOLOGICA.2020,105(6):1630-1640.doi:10.3324/haematol.2019.218289.
APA：
Tong, Jia,Xu, Xiaoguang,Zhang, Zilu,Ma, Chengning,Xiang, Rufang...&Yan, Hua.(2020).Hypoxia-induced long non-coding RNA DARS-AS1 regulates RBM39 stability to promote myeloma malignancy.HAEMATOLOGICA,105,(6)
MLA：
Tong, Jia,et al."Hypoxia-induced long non-coding RNA DARS-AS1 regulates RBM39 stability to promote myeloma malignancy".HAEMATOLOGICA 105..6(2020):1630-1640
医学