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

我的长期职业目标是成为一家学术中心的一名教职员工，在那里我将研究 microRNAs（miRNAs）在卵巢癌转移中的作用我目前的职业目标是建立一个 在控制卵巢癌基因调控的独立研究计划，获得我需要的技能， 一个独立的科学家，并获得指导和教学技能所需的教员。我是 在新墨西哥州大学的劳里哈德逊博士的实验室里进行我的研究， 获得最先进的基因组学、显微镜和流式细胞术资源。UNM是指定的NCI 癌症中心和家庭的研究人员，其合作和多学科的努力， 创造丰富的研究环境。基于她在研究教育方面的强大背景，哈德逊博士 新墨西哥大学的实验室是支持过渡到教师职位的理想环境。我的项目目标是 了解miRNAs的调节如何促进卵巢癌转移。表皮生长因子 表皮生长因子受体（EGFR）与晚期卵巢癌相关，调节细胞侵袭，促进广泛的 基因表达的变化。因此，我将研究EGFR信号对miRNAs的调控， 卵巢癌的转移进展。我假设β受体信号促进卵巢癌的发生， 通过在转录水平协调调节包括miR-125 a在内的一组miRNA来调控癌症侵袭 水平我确定EGF治疗降低了miR-125 a的表达，而miR-125 a调节了转移。 卵巢肿瘤细胞中的相关靶点。下面的具体目标将测试假设：1）调查如何 EGFR信号转导转录调节卵巢肿瘤细胞中miRNA的表达，2）评估卵巢肿瘤细胞中EGFR的表达。 miR-125 a通过调节侵袭性靶点对侵袭潜力的贡献，以及3）分析人类肿瘤 和恶性腹水中的miR-125 a表达，以确定miR-125 a的表达是否发生改变 卵巢癌这些新的研究将为miRNAs在卵巢癌中的功能作用提供证据。 相关性：绝大多数诊断为卵巢癌的女性患有晚期转移性疾病 （>70%），预后差。EGFR通路与患者预后不良密切相关。 了解microRNA在癌症中的独特调节（通过EGFR等途径）在癌症中的功能 促进肿瘤进展将能够开发新的诊断和治疗靶点。

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 skills 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. Based on her strong background in research education, Dr. Hudson's lab at UNM is the ideal environment to support by transition 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 EOF receptor signaling promotes ovarian cancer invasion by coordinately regulating a cohort of miRNAs including miR-125a at the transcriptional level. I determined that EGF treatment reduces mir125a expression and miR-125a regulates metastasis relevant targets in ovarian tumor cells. The following specific aims will test the hypothesis: 1) investigate how EGFR signaling transcriptionally regulates miRNA expression in ovarian tumor cells, 2) evaluate the contribution of miR-125a to invasive potential by regulating invasive targets, and 3) analyze human tumors and malignant ascites for miR-125a expression to establish whether the expression of miR-125a is altered in ovarian cancer. These novel studies will provide evidence for 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.