Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.


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


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.