Benzyl butyl phthalate (BBP) triggers the malignancy of acute myeloid leukemia cells via upregulation of PDK4.
Acute Myeloid Leukemia (AML) is a cancer of hematopoietic stem cells with a rapid progression. Recent studies indicated that endocrine disruptor chemicals (EDCs) are potential risk factors for AML progression. Our present data showed that an industrial endocrine disrupting chemical, Benzyl butyl phthalate (BBP), can promote the proliferation of AML cells and decrease their sensitivity to daunorubicin (DNR) and cytarabine (Ara-C) treatments. Further, BBP can increase the glucose consumption, lactate generation, and ATP levels of AML cells. Among the measured glycolysis-related genes, BBP can increase the expression of pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4), a mitochondrial protein that regulates the tricarboxylic acid cycle (TCA) cycle. The inhibitor of PDK4 or its specific siRNA can attenuate BBP-induced cell proliferation and ATP generation, which suggested the essential roles of PDK4 in BBP-induced glycolysis and proliferation. Further, BBP can increase the mRNA stability of PDK4, while had no effect on its transcription and protein stability. miR-15b-5p can bind with the 3'UTR of PDK4 to decrease its mRNA stability, while BBP can decrease the expression of miR-15b-5p in AML cells. Collectively, our data showed that BBP can trigger the malignancy of AML cells via regulation of miR-15b-5p/PDK4 signals.
['Duan|Xian-Liang|XL|', 'Ma|Cong-Cong|CC|', 'Hua|Jing|J|', 'Xiao|Tai-Wu|TW|', 'Luan|Jing|J|']
D020121:5' Untranslated Regions D000255:Adenosine Triphosphate D000903:Antibiotics, Antineoplastic D000964:Antimetabolites, Antineoplastic D002273:Carcinogens D045744:Cell Line, Tumor D049109:Cell Proliferation D003561:Cytarabine D003630:Daunorubicin D015972:Gene Expression Regulation, Neoplastic D006019:Glycolysis D006801:Humans D015470:Leukemia, Myeloid, Acute D035683:MicroRNAs D010795:Phthalic Acids D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase D034741:RNA, Small Interfering D015854:Up-Regulation
AML Proliferation Glycolysis miR-15b-5p BPA