miR-34a and miR-137 and their target proteins were found to be downregulated in Acute Lymphoblastic Leukemia cells.

BRUNO, MARTÍN A; MARTÍNEZ, CONSTANTINO; RUIZ CIANCIO, DARÍO; GONZÁLEZ-CONEJERO, ROCÍO; MESTRE, MARÍA BELÉN; VARGAS, MAURICIO; COTIGNOLA, JAVIER

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Acute Lymphoblastic Leukemia (ALL) is the most frequent cancer in children, characterized by clonal proliferation of early B- and Tlymphocyte progenitors. Up to 25% of children and more than 50% of adults suffer a relapse of the disease which significantly reduces patient?s survival. Therefore, it is important to identify new biomarkers, which can be used to improve the disease prognosis and/or to predict treatment efficacy. Non-coding RNAs have been shown to play a key role in the development and progression of tumors. Recent studies point out that aberrant miR-34a and miR-137 expression leads to an increase in cell proliferation, as well as an abnormal response to chemotherapy in various types of cancer. Thus, we aimed to elucidate the role of this two microRNAs in ALL, specifically to study their association to tumor development and disease progression. To achieve this goal, we first analyzed the expression of these two microRNAs in B-ALL and T-ALL cell lines, using normal lymphoid cells as controls. We found lower expression of miR-34a and miR-137 by RT-qPCR in cancer cell lines compared to control cells. Furthermore, we studied the main proteins regulated by these non-coding RNAs: SIRT1 and LSD1. We demonstrated by Western Blot that SIRT1 and LSD1 levels were significantly higher in ALL cell lines. Finally, we overexpressed miR34a in the ALL cell lines by transfection with an expression vector in order to confirm that the lower expression of this microRNA is associated with the tumoral phenotype. The restored levels of miR-34a resulted in a downregulation of SIRT1 protein levels and cell proliferation. Thus, these novel results provide new insight into ALL cell biology. Furthermore, these results encourage us to continue studying the role of miR-34a and miR-137 as an early diagnostic molecule or a possible effective target for disease treatment.