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MicroRNA‐144 regulates cancer cell proliferation and cell‐cycle transition in acute lymphoblastic leukemia through the interaction of FMN2
Author(s) -
Jin Jie,
Wang Yu,
Xu Yang,
Zhou Xu,
Liu Yu,
Li Xiang,
Wang Jin
Publication year - 2017
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.2898
Subject(s) - downregulation and upregulation , jurkat cells , cell cycle , cell growth , microrna , cancer research , cell culture , cell cycle checkpoint , transfection , cell , biology , microbiology and biotechnology , chemistry , immunology , t cell , biochemistry , genetics , immune system , gene
Background In the present study, we explored the functional roles of microRNA‐144 (miR‐144) upregulation and downregulation in human acute lymphoblastic leukemia (ALL). Methods Gene expression of miR‐144 was examined using the quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR) in both ALL cell lines and T‐leukemic cells of ALL patients. In ALL cell lines Molt‐3 and Jurkat cells, miR‐144 was either upregulated or downregulated through lentiviral transduction. The subsequent effects of miR‐144 upregulation or downregulation on ALL proliferation, cell‐cycle transition and in vivo xenograft were assessed. A possible downstream target of miR‐144, human formin‐2 (FMN2), was assessed by a dual‐luciferase activity assay, qRT‐PCR and western blotting. FMN2 was then overexpressed in miR‐144‐upregulated Molt‐3 and Jurkat cells to determine its effect on miR‐144 induced tumor suppression on ALL proliferation and cell‐cycle transition. Results MiR‐144 was significantly downregulated in both ALL cell lines and T‐leukemic cells of ALL patients. Lentiviral transfection successfully induced miR‐144 upregulation or downregulation in Molt‐3 and Jurkat cells without affecting cell viability. Functional assays demonstrated that miR‐144 upregulation suppressed ALL proliferation and cell‐cycle transition in vitro , as well as the growth of Jurkat xenograft in vivo , whereas miR‐144 downregulation had no functional effect on ALL development. Multiple approaches confirmed that FMN2 was the downstream target of miR‐144 in ALL. Finally, overexpressing FMN2 reversed the inhibitory effects of miR‐144‐upregulation on ALL proliferation and cell‐cycle transition. Conclusions MiR‐144 functions as a tumor suppressor in ALL, very likely through the inverse regulation of its target gene FMN2.