Disabled-2 (Dab2) is a mitogen-responsive adaptor protein playing a key role in multifaceted cellular functions, such as endocytosis, epithelial-mesenchymal transition (EMT), immune function, stem cell differentiation, oncogenesis, cell signaling, and inflammatory responses. The adenosine deaminase RNA-specific binding protein (ADAR1) is a multifunctional RNA-editing enzyme that can convert adenosine to inosine, which can modulate gene expression and cellular functions in multiple pathways, such as mRNA translation by changing codons and the subsequent protein sequence, pre-mRNA splicing by changing splice site sequences, RNA stability by altering sequence for nuclease recognition, and RNA structure-dependent functions by altering RNA-protein interactions. ADAR1 has displayed a largely pro-tumorigenesis role, especially its immunosuppressive function in cancer cells, which attributes ADAR1 as a potential novel immune checkpoint for cancer treatment. In our lab, we employed an F9 mouse teratocarcinoma stem cell differentiating model and confirmed that Dab2 is an indispensable element for retinoic acid (RA)-induced F9 cell differentiation. Interestingly, our new findings indicated that during the process of RA-induced F9 cell differentiation, both the protein levels of Dab2 and ADAR1 are significantly upregulated, and siRNA-mediated Dab2 silence results in the silence of ADAR1. In addition, results from EMT models and statistical analysis from the human TCGA database further indicated that there is a positive correlation between the expression of Dab2 and ADAR1. Our results imply that Dab2 and ADAR1 may cooperate with each other to modulate cellular functions, which will present a novel mechanism for the mechanistic study of Dab2 in tumorigenesis.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:asrf-2052 |
| Date | 25 April 2023 |
| Creators | Elam, Brianna M, Rojas, Samuel, Lightener, Janet, Jiang, Yong |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | Appalachian Student Research Forum |
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