AI Article Synopsis
- ARID1A, a key component of the SWI/SNF chromatin remodeling complex, influences tumor suppression and initiation, with its deficiency potentially leading to cancer development.
- Research shows that a lack of ARID1A increases RNA editing levels and changes editing patterns, specifically through the action of the enzyme ADAR1, which edits the CDK13 gene at new sites.
- Targeting CDK13 with inhibitors like SR-4835 may provide a therapeutic avenue for tumors with ARID1A mutations, as reducing ADAR1 activity can enhance treatment sensitivity in these cells.
Article Abstract
Background: ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is thought to play a significant role both in tumor suppression and tumor initiation, which is highly dependent upon context. Previous studies have suggested that ARID1A deficiency may contribute to cancer development. The specific mechanisms of whether ARID1A loss affects tumorigenesis by RNA editing remain unclear.
Results: Our findings indicate that the deficiency of ARID1A leads to an increase in RNA editing levels and alterations in RNA editing categories mediated by adenosine deaminases acting on RNA 1 (ADAR1). ADAR1 edits the CDK13 gene at two previously unidentified sites, namely Q113R and K117R. Given the crucial role of CDK13 as a cyclin-dependent kinase, we further observed that ADAR1 deficiency results in changes in the cell cycle. Importantly, the sensitivity of ARID1A-deficient tumor cells to SR-4835, a CDK12/CDK13 inhibitor, suggests a promising therapeutic approach for individuals with ARID1A-mutant tumors. Knockdown of ADAR1 restored the sensitivity of ARID1A deficient cells to SR-4835 treatment.
Conclusions: ARID1A deficiency promotes RNA editing of CDK13 by regulating ADAR1.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151582 | PMC |
| http://dx.doi.org/10.1186/s12915-024-01927-9 | DOI Listing |
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