1, 25-Dihydroxyvitamin D3 induces monocytic differentiation of human myeloid leukemia cells by regulating C/EBPβ expression through MEF2C. Issue 148 (April 2015)

• Record Type: Journal Article
• Authors: Zheng, Ruifang; Wang, Xuening; Studzinski, George P.
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 148(2015)
• Page Start: 132
• Page End: 137
• Publication Date: 2015-04
• Subjects: Mef2C -- Vitamin D -- AML -- Monocytic differentiation -- C/EBBβ -- CD14; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2014.11.016
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Mef2C is required for 1, 25D-induced monocytic differentiation in AML cells. Mef2C regulates CD14 expression through C/EBPβ activation at transcriptional level. Mef2C is not involved in p27 Kip1 and cyclin D1 expression in 1, 25D-treated AML cells. Abstract: Myogenic enhancer factor2 (Mef2) consists of a family of transcription factors involved in morphogenesis of skeletal, cardiac and smooth muscle cells. Among the four isoforms (Mef2A, 2B, 2C, and 2D), Mef2C was also found to play important roles in hematopoiesis. At myeloid progenitor level, Mef2C expression favors monocytic differentiation. Previous studies from our laboratory demonstrated that ERK5 was activated in 1, 25-dihydroxyvitamin D3 (1, 25D)-induced monocytic differentiation in AML cells and ERK5 activation was accompanied by increased Mef2C phosphorylation. We therefore examined the role of Mef2C in 1, 25D-induced monocytic differentiation in AML cell lines (HL60, U937 and THP1) and found that knockdown of Mef2C with small interfering RNA (siRNA) significantly decreases the expression of the monocytic marker, CD14, without affecting the expression of the general myeloid marker, CD11b. CCAAT/enhancer-binding protein (C/EBP) β, which can bind to CD14 promoter and increase its transcription, has been shown to be the downstream effector of 1, 25D-induced monocytic differentiation in AML cells. When Mef2C was knocked down, expression of C/EBPβ was reduced at both mRNA and protein levels. The protein expression levels of cell cycle regulators, p27 Kip1 and cyclin D1, were not affected by Mef2C knockdown, nor the monopoiesis related transcription factor, ATF2 (activating transcription factor 2). Thus, we conclude that 1, 25D-induced monocytic differentiation, and CD14 expression in particular, are mediated through activation of ERK5-Mef2C-C/EBPβ signaling pathway, and that Mef2C does not seem to modulate cell cycle progression.