Understanding The Role of Arglu1 In Interferon Signaling Activation In Breast Cancer

<p>In the U.S., the highest number of new cancer cases belongs to breast cancer in women, and this cancer also bears the second-highest death rate in women. Despite significant progress in breast cancer treatment that has been made in the past several decades, innovative and efficient therapies are still needed to eradicate this deadly disease. Novel cancer immunotherapy with immune checkpoint blockade (ICB) could induce long-lasting responses and improve survival in hard-to-treat malignancies. Regrettably, only a fraction of breast cancer patients respond to this highly promising strategy. To improving ICB therapy in breast cancer treatment, IFN signaling induction is a potential approach. Our results demonstrated that depletion of several RNA-binding proteins, particularly a poorly known ARGLU1, triggered type I interferon signaling in breast cancer cells. This phenomenon was also seen in mouse breast cancer cells but was not seen in normal breast epithelial cells. Furthermore, my results suggested that the loss of ARGLU1 induced accumulation of dsRNAs, which were recognized by dsRNA sensors such as RIG-I and MDA5, leading to augmented IFN signaling. To identify RNAs directly bound by ARGLU1, Halotag-fused ARGLU1 was expressed in MCF7 cells for conducting CLIP-seq. These results elucidate unappreciated regulators of type I IFN signaling in breast cancer, offering potentially new targets to overcome cancer resistance to immune checkpoint blockade therapy.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2021

Authors dc:creator

• Nguyen, Phuoc
• <p>https://orcid.org/0000-0002-2904-5582</p>

Contributors dc:contributor

• Wenbo Li, Ph.D
• Jeffrey M Rosen, Ph.D.
• Ambro van Hoof, Ph.D.

• breast cancer
• ARGLU1
• immune checkpoint blockade
• IFN
• RNA-binding proteins
• dsRNA
• RIG-I
• MDA5
• Halotag
• Genetics
• Medicine and Health Sciences
• Molecular Biology
• Molecular Genetics

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1128

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2186