2024 World Conference on Lung Cancer (WCLC) - Posters-P1.02A.01 ADAR1 Regulates Tumorigenesis and Stem Cell Properties in Non-Small Cell Lung Carcinoma

P1.02A.01 ADAR1 Regulates Tumorigenesis and Stem Cell Properties in Non-Small Cell Lung Carcinoma

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The study investigates the role of ADAR1 in non-small cell lung carcinoma (NSCLC), focusing on its potential influence on tumorigenesis and stem cell properties. ADAR1, a critical gene for A to I RNA editing, is often overexpressed in NSCLC, correlating with poor prognosis by modulating interferon (IFN) responses and dampening anti-tumor immune responses.<br /><br />The research utilized human NSCLC cell lines (A549 and H2009) and murine NSCLC cells (LM2) to explore ADAR1's impact. CRISPR/Cas9 was employed to knock out ADAR1, and subsequent analyses were conducted to assess cell proliferation, IFN signaling, tumorigenicity in vivo, and tumorsphere formation. Results revealed that the loss of ADAR1 does not affect cell growth or IFN signaling. However, ADAR1 knockout significantly reduces tumorigenicity through a T-cell-independent mechanism, as shown in both human and murine models. Specifically, neither A549 nor H2009 xenografts formed tumors in immune-deficient mice with ADAR1 knocked out.<br /><br />Furthermore, ADAR1 knockout inhibits tumorsphere formation and diminishes the expression of ALDH1A1, a marker for cancer stem cells. These findings suggest that ADAR1 plays an essential role in maintaining cancer stem cell characteristics in NSCLC.<br /><br />The study underscores ADAR1's crucial function as a mediator of the cancer stem cell phenotype in NSCLC and suggests that targeting ADAR1 could be a potential therapeutic strategy. Future research will focus on elucidating the mechanisms through which ADAR1 regulates lung cancer stem cells, understanding its role in therapeutic resistance, and developing approaches to target ADAR1 in treatments.

Asset Subtitle

Manish Patel

Meta Tag

Speaker Manish Patel

Topic Tumor Biology – Preclinical Biology

Keywords

ADAR1

non-small cell lung carcinoma

NSCLC

tumorigenesis

cancer stem cells

CRISPR/Cas9

tumorsphere formation

ALDH1A1

immune response

therapeutic strategy