Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P42345 (
mTOR
)
26,049
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 DARS-AS1/
RBM39
may, therefore, represent a novel strategy to combat myeloma.
...
PMID:Hypoxia-induced long non-coding RNA DARS-AS1 regulates RBM39 stability to promote myeloma malignancy. 3128 3
