Date of Award

2010

Degree Type

Thesis

Department

Biological, Geological and Environmental Sciences

First Advisor

Shukla, Girish

Subject Headings

Prostate -- Cytology, Prostate -- Cancer, Small interfering RNA, Androgens -- Receptors

Abstract

Prostate cancer (PCa) is one of the most prevalent forms of cancer among men in America and is second only to lung cancer as a cause of cancer-related deaths in men. Recent epidemiological study shows that one in every six men over the age of forty five is at risk of PCa. Androgen receptor (AR) plays a causative role in the development of PCa. Hormonal blockade therapy which inhibits the expression of AR eventually fails and disease progresses to fatal androgen-refractory stage from androgen-dependent stage. Therefore, novel molecular approaches which can target and block the expression of AR are required. We propose that microRNAs (miRNA) that function as negative gene regulators have potential as PCa therapeutics. Using bioinformatics methods, we have identified that human miRNA hsa-miR-488* has potential to modulate AR expression. In the present study, we have validated the target site in AR 3'UTR and established that AR is a target of Hsa-miR-488*. Our data show that the ectopically expressed hsa-miR-488* as well as the synthetic miRNA mimic can suppress the expression of luciferase activity in chimeric plasmid harboring AR3'UTR with dose dependent effects. In addition, miR-488* negatively regulated the expression of endogenous androgen receptor in PCa cells LNCaP. Thus hsa-miR-488* that function as negative gene regulators has potential as PCa therapeutics

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