miR-145诱导乳腺癌细胞凋亡分子机制的识别

发布时间：2018-03-22 09:16

本文选题：miR-145　切入点：细胞凋亡　出处：《华东师范大学》2015年博士论文　论文类型：学位论文

【摘要】：自miRN A被发现以来,业已证明miRN A在基因转录后水平通过绑定其靶位点,对细胞增殖,凋亡和肿瘤发生发挥着关键性的调控作用。因此,miRNA靶标的识别对于揭示miRNA在不同生物过程中的功能起着决定性的作用。然而,大多数miRNA的功能及其作用靶标仍未被解释。在本研究中,我们再次证实了miR-145在乳腺癌中显著下调,同时,恢复miR-145的表达水平可诱导乳腺癌细胞进入凋亡。进一步的靶标预测分析以及实验证明,miR-145通过直接靶向作用于盘状结构域受体1(DDR1),发挥介导乳腺癌细胞凋亡的作用。在miR-145失调原因的探索中,实验结果表明诱导表达后的P53可以促进miR-145的表达。因而证明P53对miR-145具有转录调控作用,P53的突变或缺失可能是miR-145在乳腺癌中异常表达的主要原因。多项研究报告表明,P53表达水平与DDR1水平显著相关。因而,本论文的结果首次表明miR-145可能是P53-DDR1这一调控关系中的重要环节。以上结论表明了miR-145在乳腺癌治疗中可能作为一种潜在治疗候选物。
[Abstract]:Since the discovery of miRN A, it has been demonstrated that miRN A proliferates cells at the post-transcriptional level by binding its target sites. Apoptosis and tumorigenesis play a key regulatory role. Therefore, the recognition of miRNA targets plays a decisive role in revealing the function of miRNA in different biological processes. Most of the functions and targets of miRNA remain unexplained. In this study, we reconfirmed that miR-145 was significantly down-regulated in breast cancer. Further target prediction analysis and experimental results showed that miR-145-145 mediated the apoptosis of breast cancer cells by directly targeting the disc domain receptor 1D D D R 1 and inducing the apoptosis of breast cancer cells by restoring the expression level of miR-145. In the exploration of the causes of miR-145 maladjustment, The results showed that p53 induced expression could promote the expression of miR-145. Therefore, the mutation or deletion of p53 could be the main reason for the abnormal expression of miR-145 in breast cancer. The expression of p53 was significantly correlated with the level of DDR1. The results of this study suggest for the first time that miR-145 may be an important link in the regulatory relationship of P53-DDR1. These results suggest that miR-145 may be a potential candidate for treatment of breast cancer.
【学位授予单位】：华东师范大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R737.9

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