m6A’s Unique and Dynamic Role in Breast Cancer Progression
Author
Dorgham, Mohammed Gamal
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This item will be available on: 2025-07-01
Abstract
Despite intense study, metastatic breast cancer is still the second leading cause of female death from cancer in the US. While many genetic lesions and environmental factors have been implicated in breast cancer progression, effective treatments are still lacking, suggesting that we are missing part of the puzzle. Epithelial to Mesenchymal Transition (EMT) is a genetic process by which breast cancer cells epithelial characteristics are changed into a more invasive and mobile mesenchymal phenotype through the downregulation of epithelial genes and pathways while simultaneously upregulating mesenchymal genes and pathways. In recent years, it has become clear that posttranscriptional regulation plays a key role in the aberrant gene expression underlying malignancy and metastasis. For example, the mRNA modification N6-methyladenosine (m6A) is involved in many post-transcriptional regulation processes including mRNA stability and translational efficiency and has been reported to be involved in many different cancer types, including breast cancer. Unfortunately, there are many characterizations of m6A’s role in not just breast cancer, but all types of cancers that are often conflicting. For this study, we characterized the effects of decreasing mRNA m6A levels by knocking down METTL3 in the MCF10 genetically defined model of breast cancer. The goal of this study was to determine if effects on proliferation and migration differed based on the stage of disease progression. Here we report that knocking down METTL3 at distinct stages of breast cancer progression indeed shows unique effects at each stage. The early-stage breast cancer line showed a more proliferative phenotype with the knockdown of METTL3 while the transformed breast cancer line showed a more migratory phenotype. Interestingly, the metastasized breast cancer cell line showed almost no effect on phenotype with the knockdown of METTL3. Furthermore, our transcriptome wide analysis of these cell lines with the knockdown of METTL3 provided us with a possible mechanism of m6A regulating EMT thus resulting in these phenotypical changes we observed. Finally, this study may begin to address the controversy of m6A’s role in cancer and suggests that m6A may have a dynamic role in cancer that depends on the stage of progression.
Subject
Date
2023-07-18
Citation:
APA:
Dorgham, Mohammed Gamal.
(July 2023).
m6A’s Unique and Dynamic Role in Breast Cancer Progression
(Doctoral Dissertation, East Carolina University). Retrieved from the Scholarship.
(http://hdl.handle.net/10342/13173.)
MLA:
Dorgham, Mohammed Gamal.
m6A’s Unique and Dynamic Role in Breast Cancer Progression.
Doctoral Dissertation. East Carolina University,
July 2023. The Scholarship.
http://hdl.handle.net/10342/13173.
April 27, 2024.
Chicago:
Dorgham, Mohammed Gamal,
“m6A’s Unique and Dynamic Role in Breast Cancer Progression”
(Doctoral Dissertation., East Carolina University,
July 2023).
AMA:
Dorgham, Mohammed Gamal.
m6A’s Unique and Dynamic Role in Breast Cancer Progression
[Doctoral Dissertation]. Greenville, NC: East Carolina University;
July 2023.
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Publisher
East Carolina University