中文摘要
乳腺癌是全世界范围内女性最常见的肿瘤，其发生发展是多因素多步骤的过程，目前其致病机制尚未完全阐明，因此寻找更多乳腺癌相关基因、阐明它们的致病机理以及发现有效的临床治疗靶点就成为亟待解决的重要课题。转录共激活因子EYA2是人类胚胎发育的关键基因之一，调控多种重要器官的发育；在恶性肿瘤中EYA2起促癌作用，已经报道EYA2与卵巢癌等恶性肿瘤的发生发展、转移、预后等密切相关；同时，EYA2具有酪氨酸磷酸酶活性，是一个放射相关基因，能在DNA损伤后使修复通路中的关键蛋白H2AX去磷酸化。EYA2作为一个多功能的癌基因，研究其在乳腺癌中的作用具有重要意义，然而目前此类研究尚未见报道。我们课题组筛选到调控EYA2的microRNA- - miR-30a和miR-338,并深入研究这两种microRNA如何通过调控EYA2而在乳腺癌的发生发展、侵袭转移和放疗中发挥作用，为乳腺癌的诊断和治疗提供新的思路。
英文摘要
Breast cancer is the most common tumor in women all over the world and brings a heavy burden to the patients and the whole society. The formation and development of breast cancer is a complex process with multi-factor and multi-step, yet the mechanism on tumorigenesis and metastasis in breast cancer has not been exactly elucidated. So the first work we should do is to discover more breast cancer related genes, elucidate theirs pathogenesis and find effective clinical therapeutic targets finally. Transcriptional coactivator EYA2 is one of the key genes in human embryonic development, which regulates a variety of important organogeny. It has been reported that EYA2 is an oncogene and it plays an important role in the growth, metastasis and prognosis in many malignant tumors such as ovarian cancer. Meanwhile, EYA2 is a radiation related gene and the tyrosine phosphatase activity of it could dephosphorylate the DNA damage-related histone H2A variant H2AX. In a word EYA2 is a multifunctional oncogene, therefore the research on the relationship between EYA2 and breast cancer is extremely meaningful. However, the similar research has not been reported so far.Therefore our group screen out the microRNAs which could regulate EYA2：miR-30 and miR-338 by molecular biology technology. We intend to investigate how these two microRNAs regulate tumor formation, invasion and metastasis in breast cancer by EYA2 and explore their effects in radiotherapy, which may provide a novel strategy for the diagnosis and treatment in breast cancer.
结题摘要
乳腺癌是全世界范围内女性最常见的肿瘤，其发生发展是多因素多步骤的过程，目前其致病机制尚未完全阐明，因此寻找更多乳腺癌相关基因、阐明它们的致病机理以及发现有效的临床治疗靶点就成为亟待解决的重要课题。转录共激活因子EYA2是人类胚胎发育的关键基因之一，调控多种重要器官的发育；在恶性肿瘤中EYA2起促癌作用，已经报道EYA2与卵巢癌等恶性肿瘤的发生发展、转移、预后等密切相关；同时，EYA2具有酪氨酸磷酸酶活性，是一个放射相关基因，能在DNA损伤后使修复通路中的关键蛋白H2AX去磷酸化。EYA2作为一个多功能的癌基因，研究其在乳腺癌中的作用具有重要意义，然而目前此类研究尚未见报道。我们课题组筛选到调控EYA2的microRNA- - miR-30a和miR-338,并深入研究这两种microRNA如何通过调控EYA2而在乳腺癌的发生发展、侵袭转移和放疗中发挥作用，为乳腺癌的诊断和治疗提供新的思路。