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

我的长期职业目标是成为一个学术中心的教员， 将研究microRNAs（miRNAs）对卵巢癌转移的贡献。我目前的职业 目标是建立一个独立的研究计划，在控制卵巢癌的基因调控，获得 我需要成为一名独立科学家的技能，并获得必要的指导和教学技能 作为教员我在纽约大学的劳里哈德逊博士的实验室里进行研究 在墨西哥，我们可以获得最先进的基因组学、显微镜和流式细胞术资源。 UNM是NCI指定的癌症中心，也是各种研究人员的家园， 多学科的努力创造了丰富的研究环境。哈德逊博士在新墨西哥大学的实验室 环境，以建立我的独立性，作为一个癌症生物学家之前过渡到教师的位置。 我的项目目标是了解miRNAs的调控如何促进卵巢癌转移。 表皮生长因子受体（EGFR）与晚期卵巢癌相关，调节细胞凋亡， 入侵，并促进基因表达的广泛变化。因此，我将研究 miRNAs通过EGFR信号在卵巢癌转移进展中的作用我假设EGFR 信号通过在转录水平调节miR-125 a促进卵巢癌侵袭， 改变了miR-125 a靶基因的调控。EGF治疗降低了miR-125 a的表达。 以下具体目标将检验该假设：1）确定EGFR信号传导如何调节mir 99 b-1。 2）评估推定的miR-125 a靶点ARID 3B对卵巢肿瘤细胞的贡献 3）分析人肿瘤和恶性腹水中miR-125 a和ARID 3B表达， 确定miR-125 a是否在人卵巢癌中发挥作用。我们的新研究将提供一个功能性的 miRNAs在卵巢癌中的作用相关性：绝大多数被诊断患有卵巢癌的女性 患有晚期转移性疾病（>70%），导致预后不良。EGFR通路强烈地 与患者预后不良相关。了解microRNA在癌症中的独特调节方式（通过 在促进肿瘤进展中的功能将使得能够开发新的肿瘤抑制剂。 诊断和治疗目标。

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.