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

我的长期职业目标是成为一名学术中心的教员，在那里我 将探讨microRNAs(MiRNAs)在卵巢癌转移中的作用。我现在的职业生涯 目标是建立一个控制卵巢癌基因调控的独立研究计划，Gain 成为一名独立科学家所需的技能，并获得必要的指导和教学技能 作为教职员工。我在纽约大学劳里·哈德森博士的实验室进行我的研究 在墨西哥，我们可以获得最先进的基因组学、显微镜和流式细胞仪资源。 UNM是美国国家癌症研究所指定的癌症中心，也是不同研究小组的所在地，他们合作 多学科的努力创造了丰富的研究环境。哈德森博士在新墨西哥州大学的实验室是理想的 在过渡到教员职位之前，我需要一个环境来确立我作为一名癌症生物学家的独立性。 我的项目目标是了解miRNAs的调控如何促进卵巢癌的转移。 表皮生长因子受体(EGFR)与晚期卵巢癌相关，调节细胞 侵袭，并促进基因表达的广泛变化。因此，我将调查监管 通过EGFR信号转导的miRNAs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-125a促进卵巢癌侵袭 改变miR-125a靶基因的调控。我确定EGF治疗降低了miR-125a的表达。 以下特定目的将检验这一假设：1)确定EGFR信号如何调节mir99b- 125a簇，2)评价可能的miR-125a靶向ARID3B对卵巢肿瘤细胞的作用 侵袭性，以及3)分析人类肿瘤和恶性腹水miR-125a和ARID3B的表达 确定miR-125a在人类卵巢癌中是否起作用。我们的小说研究将提供一种功能 MiRNAs在卵巢癌中的作用。相关性：绝大多数被诊断为卵巢癌的女性 有晚期转移性疾病(&gt；70%)导致预后不良。EGFR途径是强有力的 与糟糕的患者结局有关。了解microRNAs如何在癌症中受到独特的调控(通过 促进肿瘤进展的途径(如EGFR)将使新的 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.