Author ORCID Identifier

0009-0002-8953-5986

Date of Graduation

5-2026

Document Type

Thesis (MS)

Program Affiliation

Genetics and Epigenetics

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Angela Ting

Committee Member

Xiaodong Cheng

Committee Member

Christopher Johnston

Committee Member

Han Xu

Committee Member

Shane R. Cunha

Abstract

Effects of m6A DNA methylation by bacterial methyltransferase in colorectal cancer Fabian Alejandro Mendoza Galvan Advisory Professor: Angela H. Ting, Ph.D. Fusobacterium nucleatum animalis (Fna) is found in the human oral cavity and gut. A distinct clade of Fna is primarily enriched in the tumor microenvironment (TME) and within colorectal cancer (CRC) cells. This clade DNA methylation pattern is primarily catalyzed by a cell-cycle regulated methyltransferase (CcrM) ortholog, M.FnI, that targets the GANTC sequence motif through methyl-6-Adenine (m6A) DNA methylation. We hypothesized that M.FnI enzyme can induce m6A methylation abnormalities in CRC cells to promote cancer progression. Evidence for endogenous m6A modification in human DNA is limited and controversial so the functional impact of m6A DNA modification remains uncertain. We tested our hypothesis by ectopically expressing M.FnI in HCT116 colorectal cancer cells using expression constructs that encode either the wildtype protein (M.FnIWT) or catalytically inactive mutants (M.FnID33N and M.FnIG219R). Although considerable efforts were spent on optimizing experimental conditions, initial results indicated that M.FnI bacterial methyltransferase maintained its m6A DNA methylation capability in human HCT116 cells. Importantly, HCT116 cells could sustain expression of M.FnI methyltransferase and tolerate the presence of m6A modification in the nuclear genome. Further research is necessary to better understand how novel epigenetic modification DNA m6A may play a role in the development of gut cancer.

Keywords

Colorectal cancer, HCT116 cells, m6A DNA methylation, bacterial methyltransferase

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