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

PLC-beta 1 (PLC beta 1) 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 PLC beta 1 suppresses the differentiation of K562 elicited by MTH as demonstrated by the absence of gamma-globin expression. Inhibition of PLC beta 1 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 PLC beta 1 signaling regulates erythropoiesis through miR-210. Indeed overexpression of PLC beta 1 leads to a decrease of miR-210 expression after MTH treatment. Moreover miR-210 is up-regulated when PLC beta 1 expression is down-regulated. When we silenced PKC alpha by RNAI technique, we found a decrease in miR-210 and gamma-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 PLC beta 1. Therefore we suggest a novel role for PLC beta 1 in regulating miR-210 and our data hint at the fact that, in human K562 erythroleukemia cells, the modulation of PLC beta 1 expression is able to exert an impairment of normal erythropoiesis as assessed by gamma-globin expression.