Epidermal growth factor regulation of miR-125a promotes invasive ovarian cancer

我的长期职业目标是成为一所学术中心的教员

My long-term career goal is to become a faculty member at an academic center where I will investigate the contribution of microRNAs (miRNAs) to ovarian cancer metastasis. My current career goals are to build an independent research program in the control of ovarian cancer gene regulation, gain the skill sets I need to be an independent scientist, and acquire the mentorship and teaching skills necessary as faculty member. I am conducting my research in the lab of Dr. Laurie Hudson at the University of New Mexico where we have access to state-of-the-art genomics, microscopy, and flow cytometry resources. UNM is a NCI designated Cancer Center and home to diverse group of investigators whose collaborative and multi-disciplinary efforts generate a rich research environment. Dr. Hudson's lab at UNM is the ideal environment to establish my independence as a cancer biologist before transitioning to a faculty position. My project objective is to understand how regulation of miRNAs contributes to ovarian cancer metastasis. The Epidermal growth factor receptor (EGFR) is associated with advanced ovarian cancer, regulates cell invasion, and promotes broad changes in gene expression. Therefore, I will investigate regulation of miRNAs by EGFR signaling in the metastatic progression of ovarian cancer. I hypothesize that EGFR signaling promotes ovarian cancer invasion by regulating miR-125a at the transcriptional level resulting in altered regulation of miR-125a target genes. I determined that EGF treatment reduces miR-125a expression. The following specific aims will test the hypothesis: 1) determine how EGFR signaling regulates the mir99b- 125a cluster, 2) evaluate the contribution of the putative miR-125a target ARID3B to ovarian tumor cell invasion, and 3) analyze human tumors and malignant ascites for miR-125a and ARID3B expression to establish whether miR-125a play a role in human ovarian cancer. Our novel studies will provide a functional role for miRNAs in ovarian cancer. Relevance: The vast majority of women diagnosed with ovarian cancer have advanced metastatic disease (>70%) leading to poor prognosis. The EGFR pathway is strongly associated with poor patient outcome. Understanding how microRNAs uniquely regulated in cancer (through pathways such as EGFR) function in promoting tumor progression will enable development of novel diagnostic and therapeutic targets.