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 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
