Tong J, Xu X, Zhang Z, Ma C, Xiang R, Liu J, Xu W, Wu C, Li J, Zhan F, Wu Y, Yan H

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 HIF-1. Importantly, DARS-AS1 is required ...

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for the survival and tumorigenesis of myeloma cells both in vitro and in vivo. DARS-AS1 exerts its function by binding RBM39, which impedes the interaction between RNA-binding protein 39 (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, the knockdown of DARS-AS1 inhibits the mTOR signaling pathway, which is reversed by RBM39 overexpression. We reveals a novel HIF-1/DARS-AS1/RBM39 pathway for the pathogenesis of myeloma. Therefore, targeting DARS-AS1/RBM39 may represent a novel strategy to combat myeloma.

Date: Jul. 09, 2019

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