非编码RNA：miR-638和MEG3的功能和转化研究

发布时间：2018-04-12 17:19

本文选题：miR-638 + 自噬　；参考：《北京化工大学》2016年博士论文

【摘要】：非编码RNA近来一直是肿瘤学的研究热点,其在细胞生长、细胞调亡及各种代谢途径都具有调控作用。非编码RNA从长度上来划分可以分为3类:小于50nt、50nt到500nt、大于500nt。本课题以小于50nt的微小非编码RNA (miR-638)和大于500nt的长链非编码RNA (MEG3)为研究对象,研究了 miR-638对肿瘤细胞自噬的调控和机制,以及MEG3对肝癌细胞生长的影响。微小RNA是一类调控性非编码RNA,参与胚胎发育、肿瘤发生等众多生理和病理过程,近年研究显示微小RNA也是重要的自噬调控因子。自噬不仅可以调控细胞生长、分化以及维持内环境稳态等生物学行为,而且在肿瘤发生与演进过程中亦发挥重要作用。本课题研究发现miR-638通过抑制靶基因DACT3的表达促进食管鳞癌KYSE450细胞和乳腺癌MCF-7细胞自噬。同时,通过对细胞进行台盼蓝计数生长测定、划痕愈合实验及Transwell实验证明miR-638可以显著促进细胞的增殖、迁移和侵袭。miRNA-自噬调控紊乱可能是肿瘤及其它疾病过程中重要的分子事件,本研究将为阐明肿瘤等疾病过过程的发病机制及为探索新的治疗策略提供新思路。越来越多的研究表明长链非编码RNA(lncRNAs)在癌症生物学方面扮演非常重要的角色,在癌症的治疗方面表现出很大的潜力。本课题研究中的MEG3和正常组织比起来在癌组织中低表达或不表达,但可以调节P53靶基因的表达,和P53相互作用来抑制肿瘤细胞的增殖。我们筛选出一种肝靶向阳离子聚合物PuPGEA2,它可以和MEG3与P53形成纳米复合物 PuPGEA2/MEG3, PuPGEA2/P53 或 PuPGEA2/(MEG3+P53),能有效地抑制肝癌细胞的增殖,研究结果表明lncRNA可作为肝癌诊断、治疗、预后判断的新靶点。
[Abstract]:Noncoding RNA has been a hot topic in oncology recently. It plays a regulatory role in cell growth, cell apoptosis and various metabolic pathways.The non-coding RNA can be divided into three categories in terms of length: less than 50 NT to 500 NT and greater than 500 NT.In this study, the regulation and mechanism of miR-638 on autophagy and the effect of MEG3 on the growth of hepatoma cells were studied, which were smaller than 50nt (RNA miR-638) and longer chain uncoded RNA (MEG3) than 500nt.MicroRNAs are a class of non-coding regulatory RNAs involved in many physiological and pathological processes such as embryonic development and tumorigenesis. Recent studies have shown that microRNAs are also important autophagy regulators.Autophagy not only regulates cell growth, differentiation and homeostasis, but also plays an important role in tumorigenesis and progression.In this study, we found that miR-638 promoted autophagy of esophageal squamous cell carcinoma KYSE450 cells and breast cancer MCF-7 cells by inhibiting the expression of target gene DACT3.At the same time, the cell growth was determined by trypan blue count, scratch healing test and Transwell test showed that miR-638 can significantly promote the proliferation of cells.Migration and invasion. MiRNA-autophagy regulation disorder may be an important molecular event in the process of tumor and other diseases. This study will provide new ideas for elucidating the pathogenesis of tumor and other diseases and exploring new treatment strategies.A growing number of studies have shown that long chain noncoding RNAs lncRNAss play a very important role in cancer biology and have great potential in the treatment of cancer.Compared with normal tissues, MEG3 in this study is low or not expressed in cancer tissues, but it can regulate the expression of p53 target gene and interact with p53 to inhibit the proliferation of tumor cells.We have screened out a liver-targeted cationic polymer PuPGEA2, which can form a nano-complex PuPGEA2 / MEG3, PuPGEA2/P53 or PuPGEA2/(MEG3 P53 with MEG3 and p53, which can effectively inhibit the proliferation of hepatoma cells. The results show that lncRNA can be used as a diagnosis and therapy for HCC.A new target for prognostic judgment.
【学位授予单位】：北京化工大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R735.7

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