Date on Master's Thesis/Doctoral Dissertation

12-2021

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

States, J. Christopher

Committee Co-Chair (if applicable)

Klinge, Carolyn

Committee Member

Klinge, Carolyn

Committee Member

Wise, Sandra

Author's Keywords

arsenic exposure; MIRNA0186; tumorigenesis; chromosomal instability

Abstract

Chronic arsenic exposure through drinking water is a global health issue, affecting more than 200 million people. Arsenic is a group I human carcinogen and causes chromosomal instability (CIN). Arsenic exposure is the second most cause of skin cancer after UV radiation. MiR-186 is overexpressed in arsenic-induced squamous cell carcinoma relative to premalignant hyperkeratosis. Predicted targets of miR-186 are cell cycle regulators. Thus, we hypothesize that miR-186 overexpression drives malignant transformation of HaCaT cells by induction of CIN. Stable clones of HaCaT transfected with pEP-miR-186 expression vector or empty vector were maintained under puromycin selection were exposed to 0 or 100 nM NaAsO2 and cultured for 29 weeks. HaCaT overexpressing miR-186 and exposed to NaAsO2 showed growth ability in agar at 12 weeks and increased CIN in contrast to unexposed vector control cells. These cells also undergo epithelial to mesenchymal transition and form colonies in agar at 29 weeks. These results suggest that miR-186 overexpression exacerbates the arsenite-induced CIN and potentially is associated with accelerated skin carcinogenesis.

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