Overexpression of miR-99a promoted expansion and suppressed differentiation of hematopoietic stem/progenitor cells

Overexpression of miR-99a promoted expansion and suppressed differentiation of hematopoietic stem/progenitor cells

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Abstract MicroRNAs (miRNAs) are a class of non-coding RNAs involved in a variety of pathophysiological processes.We have previously reported that the abnormally high expression of miR-99a is associated superman headband with drug resistance and poor prognosis in acute myeloid leukemia.However, the impact of miR-99a on normal hematopoiesis is not well understood.To investigate the effect of aberrant miR-99a overexpression on hematopoietic stem and progenitor cells (HSPCs), we overexpressed miR-99a in human umbilical cord blood CD34+ cells.

We observed that miR-99a overexpression increased the proliferation, self-renewal capacity, and transplantation efficiency of HSPCs with or without a clonal hematopoiesis-associated mutation (JAK2 V617F).Meanwhile, we found that overexpression of miR-99a blocked the maturation and differentiation of granulocytes/monocytes and erythrocytes.We then identified NIPBL as a direct target caroline gardner cards sale of miR-99a.NIPBL knockdown in HSPCs showed a phenotype similar to miR-99a overexpression.

In this study, we elucidate that abnormally high expression of miR-99a can enhance the proliferative capacity of HSPCs but inhibit myeloid differentiation and maturation.Taken together, our work has uncovered important roles for miR-99a in regulating HSPCs by enhancing the proliferation and self-renewal capacity of HSPCs but inhibiting differentiation, which play important roles in leukemic transformation.