miR-720靶向DNMT3a抑制乳腺癌细胞增殖和转移的机制研究

Breast cancer is one of the most common malignancies in female cancer. The metastasis and recurrence adopted do the major prognostic factors of breast cancer patients. It shows that microRNAs are playing an important part in malignant process. we introduced that miR-720 was lower expressed in breast cancer tissues and inhibited the proliferation and matestasis of breast cancer cells. The molecular mechanism might be that miR-720 was target regulating DNMT3a so that influence methylation of proliferation and matestasis related factors. We will continue studying the relationship of miR-720, DNMT3a and cell proliferation and matestasis of breast cancer by using experiment methods of molecular biology, cell biology and immunology. This subject will discuss the relationship of miR-720 and DNMT3a in breast cancer and the molecular mechanisms by which they regulate cell proliferation and matestasis at the level of cellular functions，animal model and patient cases. It is expected to obtain evidence that miR-720 involved in regulating proliferation and matestasis of breast cancer cells.the results may provide powerful scientific basis for explaining the molecular mechanism in development of breast cancer and applying microRNAs and their targets as new makers for the clinical diagnosis and treatment.

乳腺癌是妇女最常见的恶性肿瘤之一，影响预后的主要因素是乳腺癌复发和转移。研究表明，microRNAs在乳腺癌的恶性进程中扮演重要角色。本课题组初步发现miR-720在乳腺癌组织中呈低表达，并抑制乳腺癌细胞增殖和侵袭转移,其机制可能是miR-720靶向调控DNMT3a，从而影响增殖和侵袭转移相关分子的甲基化程度。我们将进一步采用分子生物学、细胞生物学及免疫学等实验方法明确miR-720、DNMT3a与乳腺癌细胞增殖和转移的关系。本项目拟从细胞功能、动物模型及人体乳腺癌病例三个层面探讨miR-720与DNMT3a在乳腺癌发生发展中的相互关系及其参与乳腺癌细胞增殖和侵袭转移调控的分子机制，可望获得miR-720在乳腺癌中的作用及其靶向DNMT3a参与乳腺癌细胞增殖和侵袭转移调控的可靠证据，为诠释乳腺癌发生发展的分子机制和应用microRNAs及其靶点作为诊断新指标和治疗新手段提供有力的科学依据。

本课题运用分子生物学、细胞生物学、免疫学等实验方法，对miR-720参与乳腺癌细胞增殖和侵袭转移的分子机制进行了初步研究。结果发现miR-720在乳腺癌组织和细胞中均表达下调，miR-720在乳腺癌组织的表达水平与患者的淋巴结转移及预后密切相关，提高细胞乳腺癌细胞miR-720的表达水平能降低细胞的增殖和侵袭迁移能力，miR-720在从乳腺癌中分离的肿瘤相关巨噬细胞中表达下调并通过靶向GATA3抑制M2型巨噬细胞分化，对miR-720靶基因预测及验证证实DNMT3A和SRC也是miR-720的靶基因。综合上述结果，本研究为探讨miR-720参与乳腺癌发生发展的分子机制奠定了坚定的工作基础。此外，为了进一步探讨microRNA在肿瘤发生发展中的作用及机制，本项目还研究miR-451在鼻咽癌细胞浸润和转移的作用机制以及miR-212在肝癌细胞增殖和转移中的作用机制。项目共资助发表论文4篇，培养硕士生2名。项目投入经费23万元，支出19.6925万元，剩余经费3.3075万元，剩余经费计划用于本项目研究后续支出。