Poster abstracts

Poster number 69 submitted by Manju Kasaju

The Effect of a G-Quadruplex Structure in the Oct4 3’-Untranslated Region (UTR) on its Binding Interactions with miR-145-5p

Manju Kasaju (Department of Chemistry and Biochemistry, Duquesne University), Mihaela-Rita Mihailescu (Department of Chemistry and Biochemistry, Duquesne University)

Abstract:
Cancer is the second leading cause of death worldwide, claiming the lives of people of all ages. Currently, most therapeutics are successful only if the cancer is detected early and there are minimal contributing risk factors. However, given the high potency of chemotherapeutics used in treatment, there is a decrease in the quality of life, and the potential for relapse of cancer poses significant mental stress. Researchers have been trying to find a solution to this problem, focusing their attention on cancer stem cells (CSCs), which have been found in chemo-resistant cancer cells. These CSCs have been found to have high levels of Oct4, a transcription factor that has been linked to lower survival and a higher relapse rate after treatment and thus, may affect cancer progression. However, the mechanism by which Oct4 does this is still not well-understood requiring more in-depth research. Thus, this study focused on exploring the molecular mechanisms of Oct4 translational regulation which could involve the formation of a G-quadruplex (GQ) structure in the 3’-untranslated region (UTR) of Oct4 mRNA. This G-rich region of the gene also harbors a potential binding site for the microRNA (miR)-145-5p, which may be disrupted by the formation of a GQ structure. The biophysical characterization of GQ folding and its binding interactions with miR-145-5p were performed through native polyacrylamide gel electrophoresis (PAGE), circular dichroism (CD) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and UV-visible thermal denaturation spectroscopy. Our findings support the presence of a GQ in the 3’-UTR of Oct4 mRNA and implicate potential “molecular switch” defined by GQ and miR-bound states.

Keywords: Oct4, G-Quadruplex, microRNA