Date of Submission

6-2022

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

Christina Zito, Ph.D.

Keywords

Borrelia Burgdorferi, Breast Cancer, MicroRNA, Cancer Development, Dysregulation

MeSH

Borrelia burgdorferi, Breast Neoplasms, MicroRNAs

LCSH

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

Abstract

Borrelia burgdorferi is a bacterial species that causes a multisystemic, vector-borne disease known as Lyme Disease. B. burgdorferi is capable of invading host dermal tissues, wherein it can disseminate throughout the body and invade various tissues and organs. B. burgdorferi DNA has even recently been found in several breast cancer tissue types, and its presence has been associated with poor prognosis. Studies performed by our research group have found that B. burgdorferi is indeed capable of infecting normal and neoplastic mammary epithelial cells and can increase the invasiveness of breast cancer cells. This information, coupled with the knowledge that approximately 15-20% of all cancers have infectious origins, raises the question of whether B. burgdorferi might play a causative role in the development and/or progression of breast cancer. To explore the association between B. burgdorferi infection and breast cancer tumorigenesis on the molecular level, we aimed to identify biomarkers that are affected in infected breast cancer cells such as noncoding microRNAs. Numerous previous studies demonstrate that some of the same miRNAs are dysregulated in breast cancer tissues and bacteria-infected tissues, including those infected with B. burgdorferi. This suggest that miRNAs may play a role in cancer development as a result of B. burgdorferi infection. In this Thesis, the expression of miRNAs that have been associated with both breast cancer and bacterial infection were measured in various normal and cancerous breast cell lines infected with B. burgdorferi using a quantitative real-time PCR (qRT-PCR) approach. MiRNA expression levels in infected cells were compared to expression levels in uninfected control cells to identify any differential expression. Our research group also conducted total RNA sequencing on B. burgdorferi-infected and uninfected MDA-MB-231 cells to check for any differential expression of non-coding RNAs. We found multiple miRNAs, including miR-146a, miR-206, and miR-155 were differentially expressed in certain breast cell lines after being challenged with B. burgdorferi. That said, only the change in miR-146a expression in MDA-MB-231 cells was determined to be statistically significant. RNA sequencing of infected and uninfected MDA-MB-231 cells also uncovered that the MIR3142 host gene, which encodes miR-146a, is differentially expressed in infected cells, further supporting our findings. miR-146a has known roles in breast cancer tumorigenesis and has also been found to be upregulated in response to B. burgdorferi infection. This study acts as a starting point for future research aimed at identifying miRNAs that may be dysregulated in B. burgdorferi-infected breast cells and evaluating whether this dysregulation may impact breast carcinogenesis and cancer progression.

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Available for download on Tuesday, October 12, 2027

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