miR-621表达异常在乳腺癌转移复发中的作用及机制研究

MicroRNAs(miRNA) are short, 20-22 nucleotide RNA molecules that repress the translation of mRNA by base pairing to partially complementary sites in the 3'-untranslation region(3' UTR).MiRNA have diverse function, including the regulation of cellular development, differentiation, proliferation and apoptosis. Though more than 1000 miRNAs have been identified in human, much remains to be little understood about their precise cellular functions and roles in the development of disease. Recent evidences indicate that miRNAs can function as tumor suppressors or oncogenes. There are no clinically useful molecular markers to predict prognosis in the whole breast cancer population. Aberrant expression of miRNAs is involved in a number of molecular pathways which are related to the mechanisms of invasion and metastasis. Our previous study has shown the miR-621 level was higher in the population with a good prognosis than bad prognosis in breast cancer.So far we have no idea about the functions of miR-621 in relationship with prognosis of breast cancer. So, We will study the impact of miR-621 and its pathway in breast cancer relapse and metastasis in vitro and in vivo. We hope the present study would bring new ideas to breast cancer personalized therapy and prognosis prediction.

MicroRNA与肿瘤的发生、发展、转移、预后等多方面密切相关。临床上乳腺癌缺少有效的预后预测标志物，目前对miR-621的功能及在乳腺癌预后预测方面知之甚少。我们的前期研究结果提示miR-621在转移灶中的表达较原发灶低， miR-621高表达患者组的预后明显好于miR-621低表达患者组。据此推测，miR-621与乳腺癌转移复发及预后相关，可能通过miR-621在肿瘤细胞中的异常表达，进而调控肿瘤细胞的增殖、侵袭、转移能力，从而影响患者预后。我们将在前期研究的基础上，利用人乳腺癌细胞系及乳腺癌患者样本，体内、体外水平深入研究miR-621及其上下游信号传导通路在乳腺癌复发转移中的作用及具体作用机制，为乳腺癌的预后预测提供新的思路与分子标志物。

MicroRNA与肿瘤的发生、发展、转移、预后等多方面密切相关。临床上乳腺癌缺少有效的 预后预测标志物，目前对miR-621的功能及在乳腺癌预后预测方面知之甚少。我们的前期研究 结果提示miR-621在转移灶中的表达较原发灶低，miR-621高表达患者组的预后明显好于miR-621低表达患者组。据此推测，miR-621与乳腺癌转移复发及预后相关，可能通过miR-621在肿瘤细胞中的异常表达，进而调控肿瘤细胞的增殖、侵袭、转移能力，从而影响患者预后。我们在前期研究的基础上，利用人乳腺癌细胞系及乳腺癌患者样本，体内、体外水平深入研究miR-621及其上下游信号传导通路在乳腺癌复发转移中的作用及具体作用机制，明确miR-621表达上调可通过下游靶基因ITGB1有效减弱肿瘤细胞的侵袭、转移能力，延长乳腺癌患者的无病生存期(DFS)、总生存期(OS)，从而改善患者的预后。miR-621的表达水平可作为独立预测因子预测患者预后，为乳腺癌的预后预测提供新的思路与分子标志物。