miR-187-5p Regulates Cell Growth and Apoptosis in Acute Lymphoblastic Leukemia via DKK2.
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and causes a high rate of mortality in affected adults. Many subtypes of ALL exist with disruptions in distinct genetic pathways, including those regulated by miRNAs. Here we identify miR-187-5p as being highly upregulated in B-cell ALL and a driver of cellular proliferation and suppressor of apoptosis. We show that miR-187-5p directly targets the 3'-UTR of DKK2 to mediate these effects. We further determine that inhibition of DKK2 by miR-187-5p in Nalm-6 B cells leads to inappropriate activation of Wnt/β-catenin signaling. Together, these findings reveal that the miR-187-5p-DKK2 pathway regulates Wnt/β-catenin signaling, cell growth, and apoptosis. Our findings provide the first evidence of a role for miR-187-5p in promotion of B-cell ALL.
Department of Hematology, Daqing Oilfield General Hospital, Daqing, Heilongjiang Province, China.
Ye
Y
Lou
Lei
L
Liu
Lihui
L
Zhan
Xuewei
X
Wang
Hua
H
Fan
D020413:3' Untranslated Regions; D017209:Apoptosis / Q000235:genetics*; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D034622:RNA Interference; D015854:Up-Regulation; D060449:Wnt Signaling Pathway
D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C498622:DKK2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C571843:MIRN187 microRNA, human; D035683:MicroRNAs