Dale G Schaar1, Daniel J Medina, Dirk F Moore, Roger K Strair, Yi Ting. 1. University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA. schaardg@umdnj.edu
Abstract
OBJECTIVE: MicroRNAs (miRNAs) have been implicated in complex vertebrate developmental systems, such as hematopoiesis, and may play an integral role in the development of human cancers. Based on these observations, we investigated the contribution of miRNAs to acute myelogenous leukemia cell lineage-specific differentiation. MATERIALS AND METHODS: To facilitate the identification of miRNAs and their targets relevant to leukemic cell differentiation, changes miRNA expression were analyzed in the human leukemia cell line HL-60, which historically has been utilized to study lineage-specific changes in response to the differentiation agent 12-O-tetradecanoylphorbol-13-acetate (TPA). RESULTS: Using this approach, we have identified a panel of TPA-induced miRNAs that are expressed coincident with HL-60 stereotypic morphological changes characteristic of monocytic differentiation. The transferrin receptor 1(TfR-1; CD71), whose surface expression is downregulated during TPA-mediated HL-60 cell differentiation, has been identified as a target of the TPA-induced miRNA miR-320. Cell culture experiments indicate that enforced miR-320 expression can suppress TfR-1 expression and cell proliferation. CONCLUSION: TPA induces the expression of several miRNAs in HL-60 cells, one such miRNA (miR-320) contributes to downregulation of TfR-1 surface expression characteristically seen during HL-60 monocytic differentiation. Moreover, TfR-1-targeting miRNAs, such as miR-320, may have potential as novel therapeutic agents for cancer due to their inhibitory effects on cell proliferation.
OBJECTIVE: MicroRNAs (miRNAs) have been implicated in complex vertebrate developmental systems, such as hematopoiesis, and may play an integral role in the development of humancancers. Based on these observations, we investigated the contribution of miRNAs to acute myelogenous leukemia cell lineage-specific differentiation. MATERIALS AND METHODS: To facilitate the identification of miRNAs and their targets relevant to leukemic cell differentiation, changes miRNA expression were analyzed in the humanleukemia cell line HL-60, which historically has been utilized to study lineage-specific changes in response to the differentiation agent 12-O-tetradecanoylphorbol-13-acetate (TPA). RESULTS: Using this approach, we have identified a panel of TPA-induced miRNAs that are expressed coincident with HL-60 stereotypic morphological changes characteristic of monocytic differentiation. The transferrin receptor 1(TfR-1; CD71), whose surface expression is downregulated during TPA-mediated HL-60 cell differentiation, has been identified as a target of the TPA-induced miRNA miR-320. Cell culture experiments indicate that enforced miR-320 expression can suppress TfR-1 expression and cell proliferation. CONCLUSION:TPA induces the expression of several miRNAs in HL-60 cells, one such miRNA (miR-320) contributes to downregulation of TfR-1 surface expression characteristically seen during HL-60 monocytic differentiation. Moreover, TfR-1-targeting miRNAs, such as miR-320, may have potential as novel therapeutic agents for cancer due to their inhibitory effects on cell proliferation.
Authors: R Krishnan Kutty; William Samuel; Cynthia Jaworski; Todd Duncan; Chandrasekharam N Nagineni; Nalini Raghavachari; Barbara Wiggert; T Michael Redmond Journal: Mol Vis Date: 2010-08-04 Impact factor: 2.367