Epigenetic silencing of microRNA-193a contributes to leukemogenesis in t(8;21) acute myeloid leukemia by activating the PTEN/PI3K signal pathway

Li, Yonghui; Gao, Li; Luo, Xiumei; Wang, Lili; Gao, Xiao‐Ning; Wang, Wei; Sun, Jian; Dou, Liping; Li, Jingxin; Xu, Chi; Wang, Lixin; Zhou, Min‐Hang; Jiang, Mengmeng; Zhou, Jihao; Caligiuri, Michael A.; Nervi, Clara; Bloomfield, Clara D.; Marcucci, Guido; Yu, Li

doi:10.1182/blood-2012-07-444729

Cited by 147 publications

(182 citation statements)

References 25 publications

Supporting

Mentioning

146

Contrasting

Order By: Relevance

“…miR-193a represses the expression of multiple target genes such as AML1/ETO, DNMT3a, HDAC3, KIT, CCND1, and MDM2 directly (43). Database analyses also show that cyclin R cells treated with the indicated inhibitor was performed as described.…”

Section: Discussionmentioning

confidence: 99%

miR-326-Histone Deacetylase-3 Feedback Loop Regulates the Invasion and Tumorigenic and Angiogenic Response to Anti-cancer Drugs

Kim

Park

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

miR-326-Histone Deacetylase-3 Feedback Loop Regulates the Invasion and Tumorigenic and Angiogenic Response to Anti-cancer Drugs

Kim

Park

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In this study, the authors show that Aza-dC has a greater effect on reduction of cell proliferation compared differentiation-associated genes including the erythroidlineage transcription factor GATA1, which inhibits proliferation of the cancer cells [20] . A link between DNA hypermethylation and AML1/ETO-mediated repression of microRNA expression has been suggested as a means to inhibit apoptosis and differentiation of leukemic stem and progenitor cells [63,64] . In AML and chronic myeloid leukemia cell lines, Aza treatment reactivated expression of microRNA-193a, which suppresses translation of oncogenes including c-kit.…”

Section: Leukemiamentioning

confidence: 99%

Epigenetic therapy of cancer stem and progenitor cells by targeting DNA methylation machineries

Wongtrakoongate

2015

WJSC

View full text Add to dashboard Cite

Recent advances in stem cell biology have shed light on how normal stem and progenitor cells can evolve to acquire malignant characteristics during tumorigenesis. The cancer counterparts of normal stem and progenitor cells might be occurred through alterations of stem cell fates including an increase in self-renewal capability and a decrease in differentiation and/or apoptosis. This oncogenic evolution of cancer stem and progenitor cells, which often associates with aggressive phenotypes of the tumorigenic cells, is controlled in part by dysregulated epigenetic mechanisms including aberrant DNA methylation leading to abnormal epigenetic memory. Epigenetic therapy by targeting DNA methyltransferases (DNMT) 1, DNMT3Aand DNMT3B via 5-Azacytidine (Aza) and 5-Aza-2'-deoxycytidine (Aza-dC) has proved to be successful toward treatment of hematologic neoplasms especially for patients with myelodysplastic syndrome. In this review, I summarize the current knowledge of mechanisms underlying the inhibition of DNA methylation by Aza and Aza-dC, and of their apoptotic-and differentiation-inducing effects on cancer stem and progenitor cells in leukemia, medulloblastoma, glioblastoma, neuroblastoma, prostate cancer, pancreatic cancer and testicular germ cell tumors. Since cancer stem and progenitor cells are implicated in cancer aggressiveness such as tumor formation, progression, metastasis and recurrence, I propose that effective therapeutic strategies might be achieved through eradication of cancer stem and progenitor cells by targeting the DNA methylation machineries to interfere their "malignant memory". Core tip: Several types of cancers can be developed from genetic and/or epigenetic instabilities of stem and progenitor cells. Epigenetic abnormality involving dysregulation of DNA methylation has been reported to implicate in cancer aggressiveness. Inhibition of DNA methyltransferase activity by DNA methylation inhibitors has shown promising results toward treatment of myelodysplastic syndrome, a disease associated with leukemic stem cells. This review summarizes evidences which are pertinent to the antitumorigenic potential of DNA methylation inhibitors 5-Azacytidine and 5-Aza-2'-deoxycytidine on cancer stem and progenitor cells including those of leukemia and other solid tumors.Wongtrakoongate P. Epigenetic therapy of cancer stem and REVIEWSubmit a

show abstract

“…High expression of miR-100 and miR-375 was found in pediatric AML patients, which were correlated with poorer relapse-free and overall survival (14,15). miR-193a expression is downregulated in AML1/ETO-positive leukemia cells, suppression of miR193a expands the oncogenic activity of the fusion protein AML1-ETO involving a feedback circuitry in miR-193a and AML1-ETO/DNMTs/HDACs (16). Recently, increased miR181a expression was shown to be associated with improved prognosis in cytogenetically normal AML.…”

Section: Molecular Dysfunctions In Acute Myeloid Leukemia Revealed Bymentioning

confidence: 99%

Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor

Lin

Sun

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Acute myeloid leukemia (AML) is a heterogenic hematological malignancy with pathogenesis that has yet to be elucidated. MicroRNAs (miRNAs) and transcription factors (TFs) are two major regulators of gene expression, which may play important roles in the etiology of AML. However, the global regulation of gene expression in AML, involving miRNAs and TFs, still remains elusive. To characterize the global role of miRNAs and TFs in AML pathogenesis, large scale expression profiling of miRNA and TF was performed using miRNA sequencing and TF array technology, respectively, and validated by qPCR. In the present study, 308 miRNAs and 84 TFs were identified to be differentially expressed (fold-change ≥2.0) in AML samples relative to their controls. After integrating the expression profiling data into bioinformatic analysis, we identified 1,462 miRNA-gene pairs, 982 TF-gene pairs and 296 TF-miRNA pairs. By merging these regulatory relations together, we constructed a comprehensive AML-specific miRNA-TF regulatory network. In this network, we identified 22 hub miRNAs and 11 hub TFs. KEGG pathway analysis showed that the network nodes were significantly enriched in 33 different pathways, of which the AML pathway was the most significant. After analyzing the topology of the subnetwork, we propose that TCF3 was a potential key regulator in this regulatory network. In conclusion, this is the first study perform on global expression profiling of miRNAs and TFs relating to AML. These results may enhance our understanding of the molecular mechanisms underlying AML and provide potential targets for future therapeutics.

show abstract

Epigenetic silencing of microRNA-193a contributes to leukemogenesis in t(8;21) acute myeloid leukemia by activating the PTEN/PI3K signal pathway

Cited by 147 publications

References 25 publications

miR-326-Histone Deacetylase-3 Feedback Loop Regulates the Invasion and Tumorigenic and Angiogenic Response to Anti-cancer Drugs

miR-326-Histone Deacetylase-3 Feedback Loop Regulates the Invasion and Tumorigenic and Angiogenic Response to Anti-cancer Drugs

Epigenetic therapy of cancer stem and progenitor cells by targeting DNA methylation machineries

Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor

Contact Info

Product

Resources

About