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

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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.