title: ZNF300 knockdown inhibits forced megakaryocytic differentiation by phorbol and erythrocytic differentiation by arabinofuranosyl cytidine in K562 cells.
abstract: Previously, we reported that ZNF300 might play a role in leukemogenesis. In this study, we further investigated the function of ZNF300 in K562 cells undergoing differentiation. We found that ZNF300 upregulation in K562 cells coincided with megakaryocytic differentiation induced by phorbol-12-myristate-13-acetate (PMA) or erythrocytic differentiation induced by cytosine arabinoside (Ara-C), respectively. To further test whether ZNF300 upregulation promoted differentiation, we knocked down ZNF300 and found that ZNF300 knockdown effectively abolished PMA-induced megakaryocytic differentiation, evidenced by decreased CD61 expression. Furthermore, Ara-C-induced erythrocytic differentiation was also suppressed in ZNF300 knockdown cells with decreased γ-globin expression and CD235a expression. These observations suggest that ZNF300 may be a critical factor controlling distinct aspects of K562 cells. Indeed, ZNF300 knockdown led to increased cell proliferation. Consistently, ZNF300 knockdown cells exhibited an increased percentage of cells at S phase accompanied by decreased percentage of cells at G0/G1 and G2/M phase. Increased cell proliferation was further supported by the increased expression of cell proliferation marker PCNA and the decreased expression of cell cycle regulator p15 and p27. In addition, MAPK/ERK signaling was significantly suppressed by ZNF300 knockdown. These findings suggest a potential mechanism by which ZNF300 knockdown may impair megakaryocytic and erythrocytic differentiation.
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei, China; College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Jinyang
authors.initials: J
authors.lastname: Cai
authors.affiliation: Hubei International Travel Healthcare Center, Hubei Entry-Exit Inspection and Quarantine Bureau of P. R. China, Wuhan, Hubei, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gong
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Yan
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Yu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei, China; College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Mingxiong
authors.initials: M
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei, China; College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D002273:Carcinogens; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C485905:ZNF300 protein, human; D003561:Cytarabine; D013755:Tetradecanoylphorbol Acetate