m6A甲基化修饰在肿瘤发生中起着重要的作用。但其在三阴性乳腺癌中的作用尚不清楚。课题组前期工作发现: m6A“阅读器”蛋白IGF2BP3在三阴性乳腺癌中高表达；IGF2BP3可通过结合Ki67 mRNA的3’-UTR区的m6A修饰位点增强其稳定性，在三阴性乳腺癌中发挥促癌作用；let-7家族miRNA负调控三阴性乳腺癌中IGF2BP3的表达；小分子抑制剂JQ1对IGF2BP3表达具有负性调控作用。据此，我们提出假说: IGF2BP3能够通过m6A途径提高Ki67 mRNA的稳定性从而上调Ki67表达，促进三阴性乳腺癌增殖；let-7家族miRNA负性调控IGF2BP3的表达，且小分子抑制剂JQ1通过调控IGF2BP3表达，抑制三阴性乳腺癌增殖。本项目将从分子、细胞水平展开研究，并结合实验动物模型、临床样本等，深入探索IGF2BP3促进三阴性乳腺癌增殖的机制，为其治疗提供新的靶点。

m6A modification in mRNA plays important roles in human cancer development. However, the function of m6A modification in TNBC is largely unclear. In our preliminary studies, we found that IGF2BP3, an m6A modification “reader”, was expressed significantly higher in TNBC tumors； IGF2BP3 may play an oncogenic role in TNBC by recognizing the m6A modification at the 3’-UTR of Ki67 mRNA and stabilizing Ki67 mRNA； let-7 family microRNAs could negatively regulate the expression of IGF2BP3 in TNBC；Small molecule inhibitor JQ1 could inhibit IGF2BP3 expression in TNBC cells. Based on these evidences, we hypothesize that IGF2BP3 may act as an oncogene in TNBC by increasing the expression of Ki67 via stabilizing its mRNA in an m6A dependent manner. Let-7 family microRNAs can negatively regulate the expression of IGF2BP3, while JQ1 can inhibit TNBC proliferation by regulating IGF2BP3 expression. This project will explore the mechanism of IGF2BP3 regulating the occurrence and development of TNBC by molecular, cellular experiments, animal model and clinical samples, and provide new targets for its treatment.