Deciphering miRNA regulated networks controlling the Myc-PI3K crosstalk in B cells and lymphoma

microRNA（miRNAs）是一类非编码RNA，是细胞命运的重要调控因子。在B细胞谱系中，小RNA控制正常和恶性细胞的分化和存活。在淋巴瘤发病过程中，它们与癌基因合作以支持疾病的发展、维持和进展。最近，我们已经证明了转录因子c-Myc（Myc）和磷脂酰肌醇3-激酶（PI 3 K）信号通路之间的协同作用在伯基特淋巴瘤的发展，一个积极的B细胞淋巴瘤与生发中心的起源。根据我们小组的观察，我们推测miRNA的失调促进了这两种因素的转化作用。因此，在拟议的项目中，我们将集中在鉴定和表征的miRNA网络的影响成熟B细胞淋巴瘤中的Myc-PI 3 K串扰。基于非常类似于人淋巴瘤发生的新产生的小鼠模型，在肿瘤细胞和代表非转化对应物的抗原活化的B细胞中评估miRNA网络。小鼠数据将得到原发性人类淋巴瘤样本中发现的补充，我们与临床合作伙伴建立了强有力的合作。总之，我们的分析将显着提高我们的知识的分子发病机制的淋巴瘤，也可能导致创新的治疗策略在不久的将来。

MicroRNAs (miRNAs) are non-coding RNAs which are important regulators of cell fate. In the B cell lineage the small RNAs control the differentiation and survival of normal and malignant cells. During lymphoma pathogenesis they cooperate with oncogenes to support the development, maintenance and progression of the disease. Recently, we have demonstrated a synergistic effect between the transcription factor c-Myc (Myc) and the phosphatidylinositol 3-kinase (PI3K) signaling pathway in Burkitt lymphoma development, an aggressive B cell lymphoma with germinal center origin. Based on observations in our groups, we speculate that miRNA deregulation promotes the transforming effect of both factors. Thus, in the proposed project we will focus on the identification and characterization of miRNA networks which impact on the Myc-PI3K crosstalk in mature B cell lymphomas. Based on newly generated mouse models that very closely resemble human lymphomagenesis the miRNA networks are evaluated in tumor cells and antigen activated B cells that represent the non-transformed counterpart. The mouse data will be complemented by findings in primary human lymphoma samples for which we established strong collaborations with clinical partners. In summary, our analyses will significantly improve our knowledge of the molecular pathogenesis of lymphomas and might also lead to innovative therapeutic strategies in the near future.