Open AccessmiR-34b Targets HSF1 to Suppress Cell Survival in Acute Myeloid Leukemia
Author(s) -
Gangcan Li,
Yanping Song,
Yunjie Zhang,
Hao Wang,
Jia Xie
Publication year - 2016
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504016x14611963142254
Subject(s) - myeloid leukemia , cancer research , hsf1 , gene silencing , cell growth , microrna , biology , wnt signaling pathway , downregulation and upregulation , apoptosis , cell culture , regulator , leukemia , viability assay , medicine , transfection , immunology , heat shock protein , signal transduction , hsp70 , microbiology and biotechnology , gene , biochemistry , genetics
Acute myeloid leukemia (AML) is the most lethal hematological malignancy, and the occurrence of chemoresistance prevents the achievement of complete remission following the standard therapy. MicroRNAs have been extensively investigated as critical regulators of hematopoiesis and leukemogenesis, and they represent a promising strategy for AML therapy. In this study, we identified miR-34b as a novel regulator in myeloid proliferation and apoptosis of leukemic cells. We found that miR-34b was developmentally upregulated in plasma and myeloid cells of healthy subjects, while it was significantly reduced in blood samples of patients with AML and AML cell lines. Moreover, the miR-34b mimicked transfection-mediated restoration of miR-34b inhibited cell viability and promoted cell apoptosis of HL-60 and OCI-AML3 cell lines. Using a miRNA predicting algorithm miRanda, we selected a potent target heat shock transcription factor 1 (HSF1) since that is a master regulator of the heat shock response and is associated with cancer aggressiveness and dissemination. In contrast to the level of miR-34b, HSF1 was highly expressed in blood samples of patients with AML and AML cell lines. The luciferase reporter assay revealed that miR-34b directly targeted the HSF1 gene. HSF1 silencing exhibited comparable inhibitory effects on AML cell proliferation and survival. The upregulated HSF1 elevated the activation of the Wnt-β-catenin pathway. In conclusion, miR-34b suppressed AML cell proliferation and survival by targeting HSF1, in turn leading to the inactivation of Wnt-β-catenin pathway, which may highlight a new therapeutic approach for AML.