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

Alireza G. Senejani, Ph.D.

Committee Member

Anna Kloc, Ph.D.

Keywords

miRNAs, Mammary Epithelial Cells, Breast Cancer Cells

MeSH

Borrelia burgdorferi, MicroRNAs, Breast Neoplasms, Epithelial Cells

LCSH

Borrelia burgdorferi, MicroRNA, Breast--Cancer--Research, Epithelial cells

Abstract

Breast cancer is one of the leading causes of death in women worldwide. Recent studies demonstrated that inflammation due to infections with microorganisms could also result in developing breast cancer. Borrelia burgdorferi, the causative agent of Lyme disease has been shown to be present in various types of breast cancer with poor prognosis. Our research group previously published that infection of breast cancer cells B. burgdorferi results in increased in vitro migration and invasion with changes in tissue remodeling factors suggesting that B. burgdorferi could influence breast cancer tumorigenesis. To able to find markers for monitoring the genome-wide genetic changes caused by B. burgdorferi we have evaluated the microRNA expression profiles of two triple-negative breast cancer cell lines (MDA-MB-231 and HCC1806) one nontumorigenic cell line (MCF10A) before and after infection. Using a cancer-specific microRNA panel four miRNA (miRNAs 206, 214-3p, 16-5p, and 20b-5p) as potential markers for Borrelia induced changes. Additionally, miRNA 146a was added to the selection because of previous studies on B. burgdorferi-infected cells. The changes in that five-miRNA expression were confirmed by quantitative Real-Time PCR methods in all three cell lines. Statistical analyses determined that miRNAs 206 and 214 were the most significantly upregulated markers. For a better understanding of the cellular impact of those differentially expressed miRNAs, DIANA Tools software (mirPATH v.3) was used to evaluate the related pathways and the affected genes. Analyses showed that the cell cycle, cellular checkpoints, DNA damage and repair, and cancer related signaling pathways and proto-oncogenes are the most affected by B. burgdorferi infection. Hence, we identified potential miRNAs which could be further evaluated as biomarkers for tumorigenesis caused by pathogens in breast cancer cells.

Available for download on Wednesday, February 09, 2028

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