2023 World Conference on Lung Cancer (Posters)-EP02.03. ADAR1 Knockout Results in Loss of Tumorigenicity in a Syngeneic Murine Model of Non-small Cell Lung Cancer.

EP02.03. ADAR1 Knockout Results in Loss of Tumorigenicity in a Syngeneic Murine Model of Non-small Cell Lung Cancer. - PDF(Abstract)

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This study aimed to investigate the role of the RNA-editing enzyme, ADAR1, in non-small cell lung cancer (NSCLC) tumor biology. The researchers used CRISPR-Cas9 gene editing to knockout ADAR1 in human and murine NSCLC cell lines. In vitro assays showed that the loss of ADAR1 did not significantly affect cell proliferation. However, in a syngeneic murine model, where ADAR1 wild-type (WT) and knockout (KO) NSCLC cells were injected into opposite flanks of mice, the ADAR1 WT cells formed tumors with a median volume of 1692 mm3 by day 21, while only 1 out of 5 mice developed an ADAR1 KO tumor with a significantly smaller median volume of 42 mm3. The mice were sacrificed due to the large size of ADAR1 WT tumors. <br /><br />Based on these findings, the researchers concluded that the loss of ADAR1 inhibits the tumorigenicity of NSCLC cells in a syngeneic murine model without affecting cell proliferation in vitro. They hypothesized that this effect may be related to the known role of ADAR1 in IFNbeta signaling and antitumor immunity. To further investigate this hypothesis, the researchers plan to use immune-deficient mice to assess tumorigenesis in these models.<br /><br />In summary, this study demonstrates that ADAR1 plays a role in the tumorigenicity of NSCLC. The findings suggest that ADAR1 may have an impact on the tumor microenvironment, potentially influencing immune signaling and antitumor immune responses. Further research is needed to fully understand the mechanisms underlying the role of ADAR1 in NSCLC and its potential as a therapeutic target.

Asset Subtitle

Manish Patel

Meta Tag

Speaker Manish Patel

Topic Tumor Biology: Preclinical Biology - Regulatory Mechanisms

Keywords

ADAR1

NSCLC

tumor biology

gene editing

cell proliferation

tumorigenicity

IFNbeta signaling

antitumor immunity

murine model

therapeutic target