Award Date

May 2023

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Dental Medicine

First Committee Member

Karl Kingsley

Second Committee Member

Katherine Howard

Third Committee Member

Brian Chrzan

Fourth Committee Member

Maxim Gakh

Number of Pages

61

Abstract

Objective: Although progress has been made towards the identification of molecular profiles that influence oral cancer growth and metastasis, recent advances have suggested that non-coding microRNAs (such as miR-21, miR-27, miR-145, miR-155, miR-365, miR-375 and miR-494) may be involved in multiple aspects of chemotherapeutic responsiveness. Based upon the paucity of information regarding this phenomenon, this project will determine whether these specific microRNAs are correlated with oral cancer responsiveness to chemotherapies, including Paclitaxel, Cisplatin and Fluorouracil (5FU).Methods: Commercially available and well-characterized oral squamous cell carcinoma cell lines (SCC4, SCC9, SCC15, SCC25 and CAL27) were used for this study. Experimental 96-well assays were performed to determine proliferation rates, chemotherapy resistance and sensitivity. RNA was extracted under treatment conditions and relative expression of microRNAs was analyzed using qPCR to determine any correlations with chemotherapy resistance. Results: Proliferation assays revealed differing resistance and chemosensitivity to Cisplatin (-8.47% to -55.14%), Fluorouracil or 5FU (-8.5% to -57.31%) and Paclitaxol or Taxol (- 4.5% to -62.54%) among the oral cancer cell lines - with SCC9 and SCC25 demonstrating the most resistance and SCC15 the least resistance. SCC9 and SCC25 are also the only cell lines that expressed miR-375, and were the only cell lines that do not express miR-27. In addition, the least susceptible cell line SCC15 was the only cell line to express miR-145 and conversely was the only cell line not to produce miR-155. Conclusions: This study demonstrated that the most susceptible cell line to all three chemotherapeutic agents produced miR-375 but did not produce miR-27. Conversely, the least susceptible cell lines differentially expressed miR-145 and miR-155. This strongly suggests differential microRNA expression may be associated with chemotherapeutic resistance to known and commonly used agents, which may be a useful tool to determine chemoresistance potential in specific tumors - a specific goal of personalized medicine and individualized therapy. One sentence summary: Chemotherapy resistance among oral cancer cell lines was strongly correlated with differential expression of microRNAs, including miR-133, miR-27, miR-494, miR-145, miR-365, miR-720, miR-124 and miR-424. Keywords: Oral cancer, chemotherapy resistance, microRNA expression

Keywords

Chemotherapy Resistance; microRNA expression; Oral Cancer

Disciplines

Dentistry

File Format

pdf

Degree Grantor

University of Nevada, Las Vegas

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

Download


Included in

Dentistry Commons

Share

COinS