ADAR overexpression

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.

In conclusion, exercise-induced ADAR2 protects against lipogenesis during NAFLD by editing miR-34a. RNA editing mediated by ADAR2 may be a promising therapeutic candidate for NAFLD.

We found that the transcription and expression of ADAR1 was inhibited upon EV-D68 infection. RNA interference of endogenous ADAR1 decreased VP1 protein expression and viral titers, while overexpression of ADAR1p110, but not ADAR1p150, facilitated viral replication. Immunofluorescence assays showed that ADAR1p110 migrated from the nucleus to the cytoplasm after EV-D68 infection. Further, ADAR1p110 lost its pro-viral ability after mutations of the active sites in the deaminase domain, and 5'-UTR sequencing of the viral genome revealed that ADAR1p110 likely plays a role in EV-D68 RNA editing. In addition, after ADAR1 knockdown, the levels of both phosphorylated double-stranded RNA dependent protein kinase (p-PKR) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α) increased. Attenuated translation activity of the viral genome 5'-UTR was also observed in the dual-luciferase reporter assay. Lastly, the deletion of ADAR1p110 dsRBDs increased the level of p-PKR, which correlated with a decreased VP1 expression, indicating that the promotion of EV-D68 replication by ADAR1p110 is also related to the inhibition of PKR activation by its dsRBDs. Our study illustrates that ADAR1p110 is a novel pro-viral factor of EV-D68 replication and provides a theoretical basis for EV-D68 antiviral research.

Our findings established that amplification-driven ADAR1 overexpression results in overediting of KPC1 p.M8V in iCCAs, leading to progression via activation of the NF-κB signaling pathway, and suggested ADAR1-KPC1-NF-κB axis as a potential therapeutic target for iCCA.

The development of immunomodulatory drugs (IMiDs) such as lenalidomide has profound immunostimulatory effects and direct anti-MM activity; however, acquired resistance to IMiDs commonly underlies relapse, rendering MM largely incurable...The potential role of ADAR1 in modulating immunotherapeutic responses may help unravel potential resistance mechanisms and identify novel therapeutic strategies. Current studies involve elucidating the association of ADAR1 with CRBN pathway.

Interestingly, this ADAR3 mutant no longer repressed RNA editing, suggesting ADAR3 has a unique regulatory role beyond altering editing levels. Altogether, this study provides the first global view of ADAR3-bound RNAs in glioblastoma cells and identifies both a role for ADAR3 in repressing ADAR1-mediated editing and an RNA-binding dependent function of ADAR3 in regulating MAVS expression.

ADAR2 protein is an important deaminase in GBM and its amount correlates with patient prognosis.

Subsequently, we observed that tumors derived from ADAR1p110 (OE) cells showed increased invasion towards the epithelium, and increased levels of Survivin and CD-31 expressed in vascular endothelial cells. These results indicate that ADAR1 overexpression alters the expression of some key components of the canonical Wnt pathway, favoring invasion and neovascularization, possibly through activation of the β-catenin, which suggests an unknown role of ADAR1p110 in aggressiveness of TNBC tumors.

Combination of ADARB1-OE and AKT inhibitor MK2206 exerted stronger cell growth inhibition. Thus, our investigation demonstrated that low levels of ADARB1 might be a potential target in the tumorigenesis and prognostic evaluation of OC patients.

Therefore, ADAR-dependent editing contributes to maintaining elevated RBM8A protein levels in mesothelioma by counteracting MSI2-driven downregulation. A wider implication of this mechanism for the translational control of protein expression is suggested by the editing of similarly structured Alu elements in several other transcripts.

ADAR is significantly upregulated in breast cancer tissues, which may promote the progression of BC through the interaction of cancer cells, stromal cells, and immune cells. Targeting ADAR may offer new hope in treating breast cancer.

In conclusion, ADAR3 alleviated inflammation and pyroptosis of NP through targeting NLRP3, which suggested a therapeutical target for NP.

Furthermore, decreased expression of unedited miR-379, but not edited miR-379, was associated with treatment resistance, metastasis and shorter overall survival. Taken together, this study presents the first RT-qPCR assays that were demonstrated to distinguish A-to-I-edited microRNAs, and shows that they can be useful in the identification of biomarkers that previously have been masked by other isoforms.

Our study provides further evidence of the effect of ADAR1 over lncRNA expression levels, and on the participation of LINC00944 in breast cancer, suggesting to further investigate its potential role as prognostic biomarker.