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: EC:1.1.1.41 (
isocitrate dehydrogenase
)
3,101
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Arsenic trioxide (As
2
O
3
) is a promising effective chemotherapeutic agent for cancer treatment; however, how and through what molecular mechanisms the oxidative damage of As
2
O
3
is controlled remains poorly understood. Recently, the involvement of dysregulated long noncoding RNA ovarian tumor domain containing 6B antisense RNA1 (lncRNA
OTUD6B
-AS1) in tumorigenesis is established. Here, for the first time, we characterize the regulation of As
2
O
3
in the oxidative damage against bladder cancer via lncRNA
OTUD6B
-AS1. As
2
O
3
could activate lncRNA
OTUD6B
-AS1 transcription in bladder cancer cells, and these findings were validated in a xenograft tumor model. Functional assays showed that lncRNA
OTUD6B
-AS1 dramatically exacerbated As
2
O
3
-mediated oxidative damage by inducing oxidative stress. Mechanistically, As
2
O
3
increased levels of metal-regulatory transcription factor 1 (MTF1), which regulates lncRNA
OTUD6B
-AS1, in response to oxidative stress. Further, lncRNA
OTUD6B
-AS1 inhibited mitochondrial NADP
+
-dependent
isocitrate dehydrogenase
2 (IDH2) expression by stabilizing miR-6734-5p, which contributed to cytotoxicity by enhancing oxidative stress. Together, our findings offer new insights into the mechanism of As
2
O
3
-induced oxidative damage and identify important factors in the pathway, As
2
O
3
/lncRNA
OTUD6B
-AS1/miR-6734-5p/IDH2, expanding the knowledge of activity of As
2
O
3
as cancer treatment.
...
PMID:lncRNA OTUD6B-AS1 Exacerbates As
2
O
3
-Induced Oxidative Damage in Bladder Cancer via miR-6734-5p-Mediated Functional Inhibition of IDH2. 3295 48
