title: PLC-beta 1 regulates the expression of miR-210 during mithramycin-mediated erythroid differentiation in K562 cells.
abstract: PLC-beta 1 (PLCβ1) inhibits in human K562 cells erythroid differentiation induced by mithramycin (MTH) by targeting miR-210 expression. Inhibition of miR-210 affects the erythroid differentiation pathway and it occurs to a greater extent in MTH-treated cells. Overexpression of PLCβ1 suppresses the differentiation of K562 elicited by MTH as demonstrated by the absence of γ-globin expression. Inhibition of PLCβ1 expression is capable to promote the differentiation process leading to a recovery of γ-globin gene even in the absence of MTH. Our experimental evidences suggest that PLCβ1 signaling regulates erythropoiesis through miR-210. Indeed overexpression of PLCβ1 leads to a decrease of miR-210 expression after MTH treatment. Moreover miR-210 is up-regulated when PLCβ1 expression is down-regulated. When we silenced PKCα by RNAi technique, we found a decrease in miR-210 and γ-globin expression levels, which led to a severe slowdown of cell differentiation in K562 cells and these effects were the same encountered in cells overexpressing PLCβ1. Therefore we suggest a novel role for PLCβ1 in regulating miR-210 and our data hint at the fact that, in human K562 erythroleukemia cells, the modulation of PLCβ1 expression is able to exert an impairment of normal erythropoiesis as assessed by γ-globin expression.
authors: SC Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute, Bologna, Italy; Laboratory RAMSES, Rizzoli Orthopedic Institute, Bologna, Italy.
authors: Alberto
authors: A
authors: Bavelloni
authors: Alessandro
authors: A
authors: Poli
authors: Roberta
authors: R
authors: Fiume
authors: William
authors: W
authors: Blalock
authors: Alessandro
authors: A
authors: Matteucci
authors: Giulia
authors: G
authors: Ramazzotti
authors: James A
authors: JA
authors: McCubrey
authors: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors: Lucio
authors: L
authors: Cocco
authors: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors: Irene
authors: I
authors: Faenza
mesh_terms: D002454:Cell Differentiation; D041905:Erythroid Cells / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D054799:Phospholipase C beta / Q000235:genetics* / Q000378:metabolism*; D008926:Plicamycin / Q000378:metabolism*; D014162:Transfection
chemical_list: C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D054799:Phospholipase C beta; D008926:Plicamycin