PLC-beta 1 regulates the expression of miR-210 during mithramycin-mediated erythroid differentiation in K562 cells

PLC-beta 1 (PLCbeta1) 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 PLCbeta1 suppresses the differentiation of K562 elicited by MTH as demonstrated by the absence of gamma-globin expression. Inhibition of PLCbeta1 expression is capable to promote the differentiation process leading to a recovery of gamma-globin gene even in the absence of MTH. Our experimental evidences suggest that PLCbeta1 signaling regulateserythropoiesis through miR-210. Indeed overexpression of PLCbeta1 leads to a decrease of miR-210 expression after MTH treatment. Moreover miR-210 is up-regulated when PLCbeta1 expression is down-regulated. When we silenced PKC? by RNAi technique, we found a decrease in miR-210 and gamma-globin expression levels, which led to a severe slowdown of celldifferentiation in K562 cells and these effects were the same encountered in cells overexpressing PLCbeta1. Therefore we suggest a novel role for PLCbeta1 in regulating miR-210 and our data hint at the fact that, in human K562 erythroleukemiacells, the modulation of PLCbeta1 expression is able to exert an impairment of normal erythropoiesis as assessed by gamma-globinexpression.