Date on Master's Thesis/Doctoral Dissertation
8-2017
Document Type
Doctoral Dissertation
Degree Name
Ph. D.
Department
Pharmacology and Toxicology
Degree Program
Pharmacology and Toxicology, PhD
Committee Chair
States, J. Christopher
Committee Co-Chair (if applicable)
Klinge, Carolyn M.
Committee Member
Klinge, Carolyn M.
Committee Member
Rai, Shesh N.
Committee Member
Damodaran, Chendil
Committee Member
Kalbfleisch, Theodore
Author's Keywords
arsenic; arsenic-induced skin cancer; miRNA, mRNA; HaCaT cells; chronic exposure
Abstract
Arsenic is a naturally prevalent metalloid. Chronic arsenic ingestion through drinking water causes skin cancer. Arsenic-induced cancer mechanisms are not well defined. Epigenetic changes, including microRNA expression changes, might be playing a role. This dissertation investigates the impact of miRNA expression changes in arsenic-induced skin cancer. MiRNA expression was measure and compared using 3 different techniques, RTq-PCR, hybridization arrays and RNA-sequencing. MiRNAs differential expression in skin lesions was phenotype- and stage-related. Immortalized human keratinocytes (HaCaT) were transformed by chronic low arsenite exposure serving as a model for arsenic-induced skin carcinogenesis. Early changes in miRNAs and target mRNAs contribute to arsenic-induced carcinogenesis. Throughout the time course of arsenic exposure, dysregulation of cells’ growth and cancer-related pathways were identified. Comparisons between the miRNA profiles in lesions and cells predict some miRNAs may serve as biomarkers and/or therapeutic targets for arsenic-induced tumors. This dissertation provides strong evidences of epigenetic changes related to carcinogenesis in arsenic-induced skin cancer.
Recommended Citation
Al-Eryani, Laila, "MiRNA expression changes in arsenic-induced skin cancer in vitro and in vivo." (2017). Electronic Theses and Dissertations. Paper 2767.
https://doi.org/10.18297/etd/2767