miR-125a regulates cell cycle, proliferation, and apoptosis by targeting the ErbB pathway in acute myeloid leukemia.
microRNA profiling of acute myeloid leukemia patient samples identified miR-125a as being decreased. Current literature has investigated miR-125a's role in normal hematopoiesis but not within acute myeloid leukemia. Analysis of the upstream region of miR-125a identified several CpG islands. Both precursor and mature miR-125a increased in response to a de-methylating agent, Decitabine. Profiling revealed the ErbB pathway as significantly decreased with ectopic miR-125a. Either ectopic expression of miR-125a or inhibition of ErbB via Mubritinib resulted in inhibition of cell cycle proliferation and progression with enhanced apoptosis revealing ErbB inhibitors as potential novel therapeutic agents for treating miR-125a-low AML.
The Graduate School of Biomedical Sciences, University of Maine, Orono, ME, USA; Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
Melanie L
ML
Ufkin
The Graduate School of Biomedical Sciences, University of Maine, Orono, ME, USA; Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
Sarah
S
Peterson
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
Xuehui
X
Yang
Bioinformatics Support and Outreach, Vermont Genetics Network, Department of Biology and Physical Education, Norwich University, Northfield, VT, USA.
Heather
H
Driscoll
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
Christine
C
Duarte
The Graduate School of Biomedical Sciences, University of Maine, Orono, ME, USA; Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA. Electronic address: sathyp@mmc.org.
Pradeep
P
Sathyanarayana
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D018899:CpG Islands / Q000235:genetics; D000077209:Decitabine; D015973:Gene Expression Regulation, Leukemic; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018739:Oncogene Proteins v-erbB / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D000964:Antimetabolites, Antineoplastic; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D018739:Oncogene Proteins v-erbB; D000077209:Decitabine; D001374:Azacitidine
Apoptosis; Cell cycle; Methylation; Mubritinib; microRNA-125a