JWA, a novel signaling molecule, involved in the induction of differentiation of human myeloid leukemia cells.
Dysregulation of hematopoietic cellular differentiation contributes to leukemogenesis. Unfortunately, relatively little is known about how cell differentiation is regulated. JWA (AF070523) is a novel all-trans retinoic acid (ATRA) responsible gene that initially isolated from ATRA-treated primary human tracheal bronchial epithelial cells. For the notable performance achieved by ATRA in the differentiation induction therapy, we investigated the role of JWA in the induction of differentiation of human myeloid leukemia cells. Our results showed that JWA was not only regulated by ATRA but also by several other differentiation inducers such as phorbol-12-myristate-13-acetate (TPA), arabinoside (Ara-C), and hemin, involved in the mechanisms of differentiation along different lineages of myeloid leukemia cells arrested at different stages of development. Generally, JWA was up-regulated by these inducers in a time-dependent manner. Inhibition of JWA by RNA interference decreased the induced cellular differentiation. However, in NB4 cells treated with ATRA, dissimilar with others, the expression of JWA was down-regulated, and the induced cellular differentiation could be enhanced by silencing of JWA. Collectively, JWA works as a potential critical molecule, associated with multi-directional differentiation of human myeloid leukemia cells. In NB4 cells, JWA may function as a lineage-restricted gene during differentiation along the monocyte/macrophage-like or granulocytic pathway.
Huang
Shu
S
Department of Molecular Toxicology, The Jiangsu Key Laboratory of Human Functional Genomics and Applied Toxicology, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
Shen
Qun
Q
Mao
Wen-Ge
WG
Li
Ai-Ping
AP
Ye
Jian
J
Liu
Qi-Zhan
QZ
Zou
Chang-Ping
CP
Zhou
Jian-Wei
JW
D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology; D020868:Gene Silencing; D006098:Granulocytes / Q000378:metabolism; D018922:HL-60 Cells; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006427:Hemin / Q000737:chemistry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D026901:Membrane Transport Proteins; D009000:Monocytes / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism*; D020298:U937 Cells
C484566:ARL6IP5 protein, human; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D003561:Cytarabine; D014212:Tretinoin; D006427:Hemin; D013755:Tetradecanoylphorbol Acetate