Molecular Characterization of Lysine Specific Demethylase 1 (LSD1=KDM1A) in Human Ovarian Cancer

Epithelial ovarian cancer is one of the most lethal malignancies in women. There were annual 225,500 new cases and 140,200 deaths of ovarian cancer worldwide. According to the year 2010 statistics of the Department of Health, Executive Yuan, R.O.C. (Taiwan), ovarian cancer was the 8th leading cause of female cancer death in Taiwan. Till now, doctors and patients alike are frustrated by our lack of understanding of the mechanisms that caused ovarian cancer and the failure to achieve significant control of diseases. Epigenetic regulation is now shown in every aspect of health maintenance and disease development, including cancer. Lysine-specific demethylase 1 (LSD1), also known as KDM1A, converts dimethyl- or monomethyl-lysine 4 and lysine 9 of histone 3 to the unmodified state. Through such mechanisms, LSD1 regulates many physiological processes, including cell proliferation, differentiation, and tumorigenesis. LSD1 is shown important in many cancers, but its role in ovarian cancer has not been reported yet. Our preliminary findings first indicated that LSD1 was upregulated in ovarian cancer tissues and that knockdown of LSD1 suppressed growth of ovarian cancer cells. Subsequently, our microarray screening data confirmed that knockdown of LSD1 significantly regulated expression of multiple genes. With research experiences on tumor biology, autophagy, microRNA, gene expression, and proteomics in our research team, we are ready for studying the molecular mechanisms of LSD1 in ovarian cancer cells. In this 3-year project, we would like to (i) study clinical associations of LSD1 protein levels in ovarian cancer tissues and sera, (ii) delineate the functions of LSD1 in ovarian cancer cells, (iii) discover the genes that are regulated by LSD1 in ovarian cancer cells, and (iv) identify the partners of LSD1 in chromatin modification complexes that modify gene expression in ovarian cancer cells.

Project ID:PC10301-0132
External Project ID:NSC102-2628-B182-016-MY3