title: miR-92a Inhibits Proliferation and Induces Apoptosis by Regulating Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2) Expression in Acute Myeloid Leukemia.
abstract: Aberrant expression of microRNA-92a (miR-92a) has been investigated in various cancers. However, the function and mechanism of miR-92a in acute myeloid leukemia (AML) remain to be elucidated. Our data showed that miR-92a was evidently downregulated and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was remarkably upregulated in AML cell lines HL-60 and THP-1. Dual luciferase reporter assay revealed that MTHFD2 was a direct target of miR-92a. Gain- and loss-of-function analysis demonstrated that MTHFD2 knockdown or miR-92a overexpression notably inhibited proliferation and promoted apoptosis of AML cell lines. Restoration of MTHFD2 expression reversed proliferation inhibition and apoptosis induction of AML cells triggered by miR-92a. Moreover, an implanted tumor model in mice indicated that miR-92a overexpression dramatically decreased tumor growth and MTHFD2 expression in vivo. Taken together, our results suggest that miR-92a inhibits proliferation and induces apoptosis by directly regulating MTHFD2 expression in AML. miR-92a may act as a tumor suppressor in AML, providing a promising therapeutic target for AML patients.
authors.forename: Yueli
authors.initials: Y
authors.lastname: Gu
authors.forename: Jinchun
authors.initials: J
authors.lastname: Si
authors.forename: Xichun
authors.initials: X
authors.lastname: Xiao
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.forename: Shuo
authors.initials: S
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions; D000619:Aminohydrolases / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015973:Gene Expression Regulation, Leukemic; D064593:Heterografts; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D064251:Multifunctional Enzymes / Q000235:genetics*; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; C541874:MIRN92 microRNA, human; C000624959:MTHFD2 protein, human; D035683:MicroRNAs; D064251:Multifunctional Enzymes; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D000619:Aminohydrolases