title: Targeting miR-155 suppresses proliferation and induces apoptosis of HL-60 cells by targeting Slug/PUMA signal.
abstract: Recent studies have shown that high miR-155 expression was associated with poor prognosis in patients with acute myelogeneous leukemia (AML). Furthermore, targeting miR-155 results in monocytic differentiation and apoptosis. However, the exact role and mechanisms of miR-155 in human AML remains speculative. HL-60 cells were treated with anti-miR-155 for 72 h. Cell growth and apoptosis in vitro were detected by MTT, BrdU proliferation, colony formation and flow cytometry assay. The effect of anti-miR-155 on growth of HL-60 cells was also evaluated in a leukemia mouse model. Slug cDNA and PUMA siRNA trannsfection was used to assess the signal pathway. Different protein expression was detected by western blot assay and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. The results shown that targeting miR-155 resulted in a 24-fold decrease of miR-155 expression compared to negative control in the HL-60 cells. Targeting miR-155 significantly downregulated Slug and upregulated PUMA expression, and decreased HL-60 cell growth by 70% , impaired colony formation by approximately 60%, and increased HL-60 cell apoptosis by 45%. Targeting PUMA reversed miR-155 sliencing-induced proliferation and apoptosis of HL-60 cells. Restoration of Slug decreased PUMA expression. In murine engraftment models of HL-60 cells, we showed that targeting miR-155 was able to reduce tumor growth. This was accompanied with decreased Slug expression and increased PUMA expression in these tumors. Collectively, our findings strongly suggest targeting miR-155 exhibited in vivo and in vitro antileukemic activities in AML through a novel mechanism resulting in inhibition of Slug expression and increase of PUMA expression.
authors: Department of Hematology, Qingdao Women and Children's Hospital, Qingdao, China. blooddoc@126.com.
authors: Hui
authors: H
authors: Liang
authors: Department of Ophthalmology and Otorhinolaryngology, People's Hospital of Lanshan District, Rizhao, China.
authors: Ziyan
authors: Z
authors: Dong
authors: Department of Hematology, Qingdao Women and Children's Hospital, Qingdao, China.
authors: Jiang-Feng
authors: JF
authors: Liu
authors: Department of Ophthalmology and Otorhinolaryngology, People's Hospital of Lanshan District, Rizhao, China.
authors: Wei
authors: W
authors: Chuang
authors: Clinical Laboratory, People's Hospital of Zhangqiu, Jinan, Shandong, China.
authors: Li-Zhen
authors: LZ
authors: Gao
authors: Clinical Laboratory, People's Hospital of Laiwu, Laiwu, Shandong, China.
authors: Yu-Guo
authors: YG
authors: Ren
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology*; D015536:Down-Regulation; D018922:HL-60 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000502:physiology*; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C000604407:SNAI1 protein, human; D050794:STAT1 Transcription Factor; D000071250:Snail Family Transcription Factors