Functional characterization of FMNL1: a target gene in lymphoid cancer

Abstract

FMNL1, which belongs to the formin family, is highly expressed in acute lymphoblastic leukemia cell lines and mononuclear cells of chronic lymphocytic leukemia (CLL) patients (especially with poor prognosis), when compared to normal hematopoietic cells, and highly expressed in non-Hodgkin lymphoma cells, when compared to normal lymphoid tissue. Furthermore, it has been described a peptide derived from FMNL1 protein with anti-tumour activity against leukemic cells from patients with CLL. Based on these results, FMNL1 is a new candidate for target-specific therapy. To elucidate this hypothesis, we intend to use different tools (shRNA, lentiviral vector) for FMNL1 gene silencing and study its functional role in the neoplastic process. We expect to observe, through the gene silencing, an inhibition of proliferation, migration, cell aggregation and induction of apoptosis in vitro models using Jurkat and Namalwa cell lines and the involvement of PI3K/Akt pathway in this process. Additionally, we also expect to elucidate the relationship of FMNL1 protein with RhoGTPases Rac1, RhoA and Cdc42, through association studies and pull down. Notably, the realization of this project will allow the employment production of lentiviral vector at UNIFESP, Campus Diadema, for the first time and will be directly associated with orientations of undergraduate students and masters. (AU)