Date of Submission
1-2023
Document Type
Thesis
Degree Name
Master of Science in Cellular and Molecular Biology
Department
Biology and Environmental Sciences
Advisor
Eva Sapi, Ph.D.
Committee Member
Anthony Melillo
Committee Member
Alireza G. Senejani, Ph.D.
Committee Member
Christina Zito, Ph.D.
Keywords
Global Transcriptomic Analysis, Breast Cancer Cells, Lyme Disease, Differentially Expressed Genes (DEG)
MeSH
Breast Neoplasms, Borrelia burgdorferi, RNA
LCSH
Breast--Cancer--Research, Borrelia burgdorferi, Cancer cells, RNA
Abstract
The bacterial spirochete Borrelia burgdorferi, the causative agent of Lyme Disease, can disseminate to and colonize various tissues and organs to orchestrate a multitude of clinical symptoms including arthritis, carditis, and neuroborreliosis. Previous research has demonstrated that cancer cells provide an ideal habitat for diverse populations of bacteria, including B. burgdorferi, which presented with a poor prognosis. Additionally, preliminary studies conducted at the Lyme Disease Research Lab have demonstrated that infection with B. burgdorferi enhances the invasive and migratory capabilities of the triple-negative MDA-MB-231 cells; however, the molecular mechanisms that the pathogen recruits to bring about these more severe breast cancer phenotypes have not been extensively studied.
In this study, we hypothesized that infection by B. burgdorferi alters the expression of cancer-associated genes to effectuate more aggressive breast cancer phenotypes. We implied the high-throughput technique of RNA-Sequencing on B. burgdorferi-infected MDA-MB-231 and the normal-like MCF10A to determine the genes that were differentially expressed upon infection. Overall, 142 DEGs between uninfected and infected samples were identified in MDA-MB-231 cells (p < 0.01), while 95 DEGs were identified in MCF10A. For MDA-MB-231, 40 genes, and for MCF10A, 11 genes were differentially expressed by over 2-fold. The DEGs with a FC ≥ 3 for MDA-MB-231 and FC ≥ 2 for MCF10A were validated using qRT-PCR. Ontological analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) revealed the involvement of DEGs in pathways associated with infection, inflammation, and cancer. This study highlighted cancer-associated genes that are impacted upon infection with B. burgdorferi which could serve as potential biomarkers that the pathogen uses to enhance tumorigenesis and cancer progression can open new therapeutic opportunities.
Recommended Citation
Khatri, Vishwa, "Global Transcriptomic Analysis of Breast Cancer Cells Infected with Borrelia burgdorferi" (2023). Master's Theses. 188.
https://digitalcommons.newhaven.edu/masterstheses/188