项目名称： miR-211调控的lncRNA(s)鉴定及其在皮肤黑色素瘤发生发展中的作用研究

项目编号： No.81502365

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 徐妍

作者单位： 南京医科大学

项目金额： 18万元

中文摘要： 皮肤黑色素瘤是一种侵袭性很高的恶性肿瘤，发生转移的黑色素瘤因缺乏有效的治疗手段而预后极差。我们先前的研究显示miR-211在黑色素瘤细胞和组织中非常一致的低表达；通过提高其在黑色素瘤的表达发现肿瘤细胞的侵袭力显著下降，提示miR-211在黑色素瘤中肿瘤抑制因子的作用。近期研究发现lncRNA可作为微小RNA的靶分子起到致瘤或抑瘤的作用，并成为新的肿瘤标志物和治疗靶点。因此，本课题将通过1）lncRNA基因芯片技术筛选受miR-211调控的与黑色素瘤发生发展相关的lncRNA(s)；2）qPCR和原位杂交技术鉴定目标lncRNA(s)在黑色素瘤的表达；3）一系列功能实验对目标lncRNA(s)表达调控后的黑色素瘤细胞进行肿瘤增生、凋亡及侵袭转移等的作用研究。该课题旨在寻找与miR-211相关的靶lncRNA(s)并深入研究目标lncRNA(s)的作用，从而为黑色素瘤的治疗提供新的研究方向。

中文关键词： 黑色素细胞肿瘤；微小RNA-211；长链非编码RNA

英文摘要： Cutaneous melanoma is a highly invasive cancer. Advanced melanoma patients have poor prognosis due to the lack of effective therapies. Our earlier studies have already shown that the expression of miR-211 is greatly decreased in both melanoma cells and melanoma tissue samples compared to melanocytes and benign nevi. Moreover, our other studies also find that ectopic overexpression of miR-211 in melanoma cells repressed both colony formation in methylcellulose and migratory ability in matrigel, an in vitro surrogate assay for invasiveness. These findings indicate that miR-211 acts as tumor suppressors in melanomagenesis. Recent studies have shown lncRNAs being targets of microRNAs mediate oncogenic or tumor-suppressing effects and may be a new class of cancer biomarkers and therapeutic targets. Thus, this project tries 1) to screen miR-211 regulated lncRNA(s) that influence the melanomagenesis through lncRNA microarray, 2) to verify the selected lncRNA(s) in melanoma through qPCR and ISH, 3) to characterize the functions of the selected lncRNA(s) in melanoma progression by cell proliferation, apoptosis and migration efficacy tests. This project aims to look for miR-211 regulated lncRNA(s) and investigate their roles in melanoma development and progression, which potentially offers a novel therapeutic strategy for melanoma patients.

英文关键词： Melanoma;miR-211;Long non-coding RNA