中文摘要
随着基因组学研究的深入,近年来长非编码RNA(lncRNA)在肿瘤相关调控网络中的重要性逐渐凸显。课题组前期研究发现lncRNA-DLEU1在胃癌中高表达且与肿瘤大小等恶性表型显著相关,敲减DLEU1可抑制胃癌细胞增殖和转移。生物信息学分析结果表明DLEU1序列区域存在miR-200b/429等多种miRNAs的结合位点。我们推测DLEU1可能作为miRNA的内源竞争性RNA,介导miR-200b/429靶基因调控胃癌恶性进程。本项目中,我们将利用体内外功能实验进一步明确DLEU1在胃癌中的功能;利用生物信息学分析、分子生物学和功能学实验鉴定DLEU1与miR-200b/429的结合,阐明“DLEU1-miRNA-靶基因”在胃癌中的作用机制;在临床样本中检测相关分子表达分析其临床转化价值。本研究可丰富DLEU1在肿瘤恶性生物学行为中的功能及机制理论,为胃癌的精准治疗提供理论依据和新的方向。
英文摘要
In recent years, along with the development of genomics research, the importance of long non-coding RNA (lncRNA) in tumor related regulation network become more and more prominent. In our previous study, we identified lncRNA - DLEU1 was upregulated in gastric cancer (GC) tissues compared with adjacent normal tissues, and high expression of DLEU1 was significantly associated with malignant phenotype such as tumor size, etc. Knocking-down of DLEU1 inhibits the GC cell proliferation and metastasis. Moreover, bioinformatics analysis results show that a there exists a variety of miRNA binding sites in the sequence areas of DLEU1, including miR-200b/429.We speculated that DLEU1 may function as endogenous competitive RNA (ceRNA) of microRNAs, regulated the target gene of miRNA, and then mediate the GC malignant processes. In this project, we will further defined the function of DLEU1 in GC by using in vivo and in vitro experiments; identify the combination of DLEU1 and miR-200b/429, clarify the potential "DLEU1-miR-200b/429-target genes" signaling in GC by using bioinformatics analysis, molecular biology techniques, and function experimental; and detect the expression level of all those molecules in clinical samples, to analyze their clinical value. This study can help to clarify the functions and mechanism of DLEU1 in the development of tumor, shed new light on the accurate treatment of gastric cancer.
