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

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Alberto Bavelloni (Creator)

William Blalock (Creator)

Lucio Cocco (Creator)

Irene Faenza (Creator)

Roberta Fiume (Creator)

Alessandro Matteucci (Creator)

James A. McCubrey (Creator)

Alessandro Poli (Creator)

Giulia Ramazzotti (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: PLC-beta 1 (PLCß1) 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 PLCß1 suppresses the differentiation of K562 elicited by MTH as demonstrated by the absence of ?-globin expression. Inhibition of PLCß1 expression is capable to promote the differentiation process leading to a recovery of ?-globin gene even in the absence of MTH. Our experimental evidences suggest that PLCß1 signaling regulates erythropoiesis through miR-210. Indeed overexpression of PLCß1 leads to a decrease of miR-210 expression after MTH treatment. Moreover miR-210 is up-regulated when PLCß1 expression is down-regulated. When we silenced PKCa by RNAi technique, we found a decrease in miR-210 and ?-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 PLCß1. Therefore we suggest a novel role for PLCß1 in regulating miR-210 and our data hint at the fact that, in human K562 erythroleukemia cells, the modulation of PLCß1 expression is able to exert an impairment of normal erythropoiesis as assessed by ?-globin expression.

Additional Information

Publication

Other

Oncotarget; 5:12 p. 4222-4231

Language: English

Date: 2014

Keywords

phospholipase Cß1, K562, erythropoiesis, ?-globin, miR-210

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