ADAR overexpression

We found that the expression of ADAR1 is upregulated in GBM and is associated with tumor grade and TMZ resistance. Elevated expression of ADAR1 predicts poor prognosis in GBM patients and promotes tumor growth in vivo or in vitro.

Herein, we clarified the underlying mechanism involving the SNORD113-3/ADAR2/PHKA2/EBF1 pathway in the regulation of GBM cell growth and glycolipid metabolism. Our results provide a framework for the development of innovative therapeutic interventions to improve the prognosis of patients with GBM.

A rat epilepsy model was induced in vivo using lithium chloride-pilocarpine...In the recovery experimental group that involved silencing Kv1.1, the beneficial effects of overexpressing ADAR2 were no longer observed (P < 0.05). Our findings confirm that the upregulation of ADAR2 promotes Kv1.1 protein expression, which ultimately reduces neuronal damage in the hippocampus of animals with epilepsy.

In summary, we report the involvement of ADAR1-regulated dsRNA-sensing in modulating lenalidomide sensitivity in MM. These findings highlight a novel RNA-related mechanism underlying lenalidomide resistance and underscore the potential of targeting ADAR1 as a novel therapeutic strategy.

Finally, RNA immunoprecipitation combined with qPCR (RIP-qPCR) showed that ADAR1 binds to PAX7 and MyoD mRNA. This study indicates that ADAR1 promotes the myogenic development of goat MuSCs, which provides a useful scientific reference for further exploring the ADAR1-related regulatory networks underlying mammal skeletal muscle growth.

Furthermore, it elucidated the molecular mechanism underlying the protective effect of ADAR1, the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt)/mammalian target of the rapamycin (mTOR) signaling...The upregulation of ADAR1 expression alleviated high-glucose-induced endoplasmic reticulum stress, reduced HK-2 cell apoptosis, and reduced the expression of inflammation-related indicators (PI3K/AKT/mTOR). Taken together, the pivotal roles of ADAR1 in the progression of proximal renal tubulopathy and the mechanism of high-glucose-induced HK-2 injury in diabetic db/db mice suggest that ADAR1 may be a potential key factor in slowing the progression of diabetic kidney disease.

The current study unveils that ADAR1 is required for survival and oxidative stress of HCC cells, and targeting ADAR1 may sensitize HCC cells to oxidative stress via modulating Keap1/Nrf2 pathway.

Our pre-clinical experiments utilizing RNA-seq, a novel ADAR1-nano-luciferase-GFP reporter, and aNBM PDX mouse models provide compelling evidence supporting the potential of Rebecsinib to restore the balance of ADAR1p150:p110 ratios and engraftment in humanized aNBM HSPC mouse models. These findings highlight Rebecsinib as a promising therapeutic candidate for targeting leukemia and myelofibrosis while preserving essential HSPC populations.

We did not see a disease potentiating or modifying effect of overexpressing ADAR1 or its isoforms in the models assessed. We conclude that increased ADAR1 expression and A-to-I editing in cancers is most likely a consequence of tumor formation.