Lee King Yiu, Chan Kathy Yuen Yee, Tsang Kam Sze, Chen Yang Chao, Kung Hsiang-fu, Ng Pak Cheung, Li Chi Kong, Leung Kam Tong, Li Karen
Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong.
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
PLoS One. 2014 Mar 27;9(3):e92706. doi: 10.1371/journal.pone.0092706. eCollection 2014.
Makorin-2 (MKRN2) is a highly conserved protein and yet its functions are largely unknown. We investigated the expression levels of MKRN2 and RAF1 in normal and malignant hematopoietic cells, and leukemia cell lines. We also attempted to delineate the role of MKRN2 in umbilical cord blood CD34+ stem/progenitor cells and K562 cell line by over-expression and inhibition of MKRN2 through lentivirus transduction and shRNA nucleofection, respectively. Our results provided the first evidence on the ubiquitous expression of MKRN2 in normal hematopoietic cells, embryonic stem cell lines, primary leukemia and leukemic cell lines of myeloid, lymphoid, erythroid and megakaryocytic lineages. The expression levels of MKRN2 were generally higher in primary leukemia samples compared with those in age-matched normal BM cells. In all leukemia subtypes, there was no significant correlation between expression levels of MKRN2 and RAF1. sh-MKRN2-silenced CD34+ cells had a significantly lower proliferation capacity and decreased levels of the early stem/progenitor subpopulation (CFU-GEMM) compared with control cultures. Over-expression of MKRN2 in K562 cells increased cell proliferation. Our results indicated possible roles of MKRN2 in normal and malignant hematopoiesis.
Makorin-2(MKRN2)是一种高度保守的蛋白质,但其功能在很大程度上尚不清楚。我们研究了MKRN2和RAF1在正常和恶性造血细胞以及白血病细胞系中的表达水平。我们还试图通过分别通过慢病毒转导和shRNA核转染过表达和抑制MKRN2,来阐明MKRN2在脐带血CD34 +干/祖细胞和K562细胞系中的作用。我们的结果首次证明了MKRN2在正常造血细胞、胚胎干细胞系、原发性白血病以及髓系、淋巴系、红系和巨核细胞系白血病细胞系中的普遍表达。与年龄匹配的正常骨髓细胞相比,原发性白血病样本中MKRN2的表达水平通常更高。在所有白血病亚型中,MKRN2和RAF1的表达水平之间均无显著相关性。与对照培养物相比,sh-MKRN2沉默的CD34 +细胞具有明显更低的增殖能力,并且早期干/祖细胞亚群(CFU-GEMM)水平降低。MKRN2在K562细胞中的过表达增加了细胞增殖。我们的结果表明MKRN2在正常和恶性造血过程中可能发挥作用。