miR-34b Targets HSF1 to Suppress Cell Survival in Acute Myeloid Leukemia

Li, Gangcan; Song, Yanping; Zhang, Yunjie; Wang, Hao; Xie, Jia

doi:10.3727/096504016x14611963142254

Cited by 17 publications

(17 citation statements)

References 23 publications

(17 reference statements)

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“…Many researchers have investigated the role of miR-34 family in leukemia, especially miR-34a. For instance, Li et al reported that miR-34b was significantly lower expressed in AML blood samples and AML cell lines, and miR-34b inhibited cell viability and promoted cell apoptosis in AML cells by targeting HSF1 [27]. Yang et al showed that miR-34c was lower expressed and served as a biomarker in predicting prognosis in patients with AML [28].…”

Section: Discussionmentioning

confidence: 99%

MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

Liu

Ren

Chen

2017

Cell Physiol Biochem

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Background: MiR-34a is identified as a tumor suppressor gene and involved in acute myeloid leukemia (AML) development. However, the regulatory mechanism of miR-34a in AML is unclear. Methods: The expression of miR-34a and HMGB1 in HL-60, THP-1 and HS-5 cells were detected by qRT-PCR and western blot. Lipofectamine 2000 was used to transfect with miR-34a mimics, miR-34a inhibitor, si-HMGB1, pcDNA 3.1-HMGB1, and corresponding controls. The apoptosis and autophagy of transfected AML cells were assessed by flow cytometry and western blot, respectively. Bioinformatics software and dual luciferase reporter assay were applied to predict and verify the target of miR-34a. The effects of miR-34a mimics or si-HMGB1 on chemotherapy-induced autophagy were further explored in HL-60 cells treated with all-trans retinoic acid (ATRA) along with lysosomal protease inhibitors E64d and pepstatin A. Results: MiR-34a was lower expressed and HMGB1 mRNA and proteins were both higher expressed in HL-60 and THP-1 cells compared with that in HS-5 cells. Higher expression levels of MiR-34 and lower expression levels of HMGB1 both significantly promoted apoptosis and inhibited autophagy in HL-60 and THP-1 cells. Dual luciferase reporter system confirmed that HMGB1 was a potential target of miR-34a. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by higher expression level of miR-34a. Higher expression level of miR-34a and lower expression level of HMGB1 both inhibited chemotherapy-induced autophagy by stimulating the LC3 conversion. Conclusion: MiR-34a promoted cell apoptosis and inhibited autophagy by targeting HMGB1. Therefore, miR-34a may be a potential promising molecular target for AML therapy.

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Section: Discussionmentioning

confidence: 99%

MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

Liu

Ren

Chen

2017

Cell Physiol Biochem

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“…ASS1 (Argininosuccinate synthetase 1) gene product is responsible for the process of arginine biosynthesis; however, Miraki-Moud et al (34), reported that most AML lacked ASS1 expression, which may be due to small sample size and the different detection methods. Other genes, such as HSF1 (Heat-shock transcription factor 1), WT1 (Wilms tumor 1), ACTA2 (Actin, alpha 2), SLC15A2 (Solute carrier family 15 member 2), PDLIM1 (C terminal LIM domain protein 1), and CTSA (Cathepsin A) were revealed by our meta-analysis, and even some of them have been reported previously with increased expression in AML and MDS (35,36), their potential as diagnostic or prognostic markers in MDS and AML needs further exploration. Among the top ten downregulated DEGs, although MME encoded protein MMP12 was believed to be related with acute lymphocytic leukemia (ALL) diagnosis (37), its role in MDS and AML remains to be demonstrated.…”

Section: Discussionsupporting

confidence: 50%

Integrated bioinformatic analysis of microarray data reveals shared gene signature between MDS and AML

et al. 2018

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Myeloid disorders, especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), cause significant mobility and high mortality worldwide. Despite numerous attempts, the common molecular events underlying the development of MDS and AML remain to be established. In the present study, 18 microarray datasets were selected, and a meta-analysis was conducted to identify shared gene signatures and biological processes between MDS and AML. Using NetworkAnalyst, 191 upregulated and 139 downregulated genes were identified in MDS and AML, among which, PTH2R, TEC, and GPX1 were the most upregulated genes, while MME, RAG1, and CD79B were mostly downregulated. Comprehensive functional enrichment analyses revealed oncogenic signaling related pathway, fibroblast growth factor receptor (FGFR) and immune response related events, ‘interleukine-6/interferon signaling pathway, and B cell receptor signaling pathway’, were the most upregulated and downregulated biological processes, respectively. Network based meta-analysis ascertained that HSP90AA1 and CUL1 were the most important hub genes. Interestingly, our study has largely clarified the link between MDS and AML in terms of potential pathways, and genetic markers, which shed light on the molecular mechanisms underlying the development and transition of MDS and AML, and facilitate the understanding of novel diagnostic, therapeutic and prognostic biomarkers.

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“…In addition, HSF1 regulates HSPs to maintain the protein balance, thereby inhibiting apoptosis of multiple myeloma cells [22]. HSF1 also regulates the classical Wnt-β-catenin signaling pathway in the inhibition of acute lymphoma cell apoptosis [23]. In the present study, protein chip analysis revealed that SMAC-mediated mitochondrial apoptosis-related proteins were the most significantly enriched in pancreatic cancer cell apoptosis.…”

Section: Discussionmentioning

confidence: 64%

Heat shock factor 1 inhibits the mitochondrial apoptosis pathway by regulating second mitochondria-derived activator of caspase to promote pancreatic tumorigenesis

Liang

Liao

Zhang

et al. 2017

J Exp Clin Cancer Res

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BackgroundAs a relatively conservative transcriptional regulator in biological evolution, heat shock factor 1 (HSF1) is activated by, and regulates the expression of heat shock proteins (HSPs) in response to a variety of stress conditions. HSF1 also plays a key role in regulating the development of various tumors; however, its role in pancreatic cancer and the specific underlying mechanism are not clear.MethodsWe first examined HSF1 expression in pancreatic cancer tissues by immunohistochemistry, and then studied its clinical significance. We then constructed HSF1-siRNA to investigate the potential of HSF1 to regulate apoptosis, proliferation and the cell cycle of pancreatic cancer cells and the underlying mechanism both in vitro and in vivo. Protein chip analysis was used subsequently to explore the molecular regulation pathway. Finally, second mitochondria-derived activator of caspase (SMAC)-siRNA was used to validate the signaling pathway.ResultsHSF1 was highly expressed in pancreatic cancer tissues and the level of upregulation was found to be closely related to the degree of pancreatic cancer differentiation and poor prognosis. After HSF1-silencing, we found that pancreatic cancer cell proliferation decreased both in vitro and in vivo and the apoptotic cell ratio increased, while the mitochondrial membrane potential decreased, and the cells were arrested at the G0/G1 phase. In terms of the molecular mechanism, we confirmed that HSF1 regulated SMAC to inhibit mitochondrial apoptosis in pancreatic cancer cells, and to promote the occurrence of pancreatic tumors. SMAC silencing reversed the effects of HSF1 silencing.ConclusionOur study provides evidence that HSF1 functions as a novel oncogene in pancreatic tumors and is implicated as a target for the diagnosis and treatment of pancreatic cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0537-x) contains supplementary material, which is available to authorized users.

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miR-34b Targets HSF1 to Suppress Cell Survival in Acute Myeloid Leukemia

Cited by 17 publications

References 23 publications

MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

Integrated bioinformatic analysis of microarray data reveals shared gene signature between MDS and AML

Heat shock factor 1 inhibits the mitochondrial apoptosis pathway by regulating second mitochondria-derived activator of caspase to promote pancreatic tumorigenesis

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