Methylation-mediated repression of microRNA-143 enhances MLL–AF4 oncogene expression

Dou, Liping; Zheng, Daoyuan; Li, J; Li, Y; Gao, Li; Wang, Lili; Yu, Li

doi:10.1038/onc.2011.248

Cited by 55 publications

(46 citation statements)

References 32 publications

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“…4,36 mir-143 has been reported to repress the oncogenic MLL-AF4 fusion protein. 37 In contrast, our data from different models in vitro and in vivo support the notion that mir-139 commonly acts as a growth inhibitory molecule. Accordingly, mir-139 is silenced in a number of solid tumors including hepatocellular carcinomas, gastric and metastatic breast cancers, laryngeal squamous cell carcinoma or glioma.…”

Section: Discussionsupporting

confidence: 55%

miR-139-5p controls translation in myeloid leukemia through EIF4G2

et al. 2015

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MicroRNAs (miRNAs) are crucial components of homeostatic and developmental gene regulation. In turn, dysregulation of miRNA expression is a common feature of different types of cancer, which can be harnessed therapeutically. Here we identify miR-139-5p suppression across several cytogenetically defined acute myeloid leukemia (AML) subgroups. The promoter of mir-139 was transcriptionally silenced and could be reactivated by histone deacetylase inhibitors in a dose-dependent manner. Restoration of mir-139 expression in cell lines representing the major AML subgroups (t[8;21], inv[16], mixed lineage leukemia-rearranged and complex karyotype AML) caused cell cycle arrest and apoptosis in vitro and in xenograft mouse models in vivo. During normal hematopoiesis, mir-139 is exclusively expressed in terminally differentiated neutrophils and macrophages. Ectopic expression of mir-139 repressed proliferation of normal CD34(+)-hematopoietic stem and progenitor cells and perturbed myelomonocytic in vitro differentiation. Mechanistically, mir-139 exerts its effects by repressing the translation initiation factor EIF4G2, thereby reducing overall protein synthesis while specifically inducing the translation of cell cycle inhibitor p27(Kip1). Knockdown of EIF4G2 recapitulated the effects of mir-139, whereas restoring EIF4G2 expression rescued the mir-139 phenotype. Moreover, elevated miR-139-5p expression is associated with a favorable outcome in a cohort of 165 pediatric patients with AML. Thus, mir-139 acts as a global tumor suppressor-miR in AML by controlling protein translation. As AML cells are dependent on high protein synthesis rates controlling the expression of mir-139 constitutes a novel path for the treatment of AML.

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Section: Discussionsupporting

confidence: 55%

miR-139-5p controls translation in myeloid leukemia through EIF4G2

et al. 2015

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“…Combined with other miRNAs, plasma miR-21 could be a novel method for early cancer diagnosis. However, miR-143 usually shows a decreased expression and is considered as a cancer suppressor (104,130,131). Erb-b2 receptor tyrosine kinase 3 (ERBB3), one of the four members of the ERBB family of receptor tyrosine kinases, is targeted by miR-143, which in turn prevents breast cancer cells from proliferation and invasion.…”

Section: Clinical Significance Controversies and Future Outlookmentioning

confidence: 99%

Genetic alterations and epigenetic alterations of cancer-associated fibroblasts

Che

2016

Oncology Letters

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Cancer-associated fibroblasts (CAFs) are one major type of component identified in the tumor microenvironment. Studies have focused on the genetic and epigenetic status of CAFs, since they are critical in tumor progression and differ phenotypically and functionally from normal fibroblasts. The present review summarizes the recent achievements in understanding the gene profiles of CAFs and pays special attention to their possible epigenetic alterations. A total of 7 possible genetic alterations and epigenetic changes in CAFs are discussed, including gene differential expression, karyotype analysis, gene copy number variation, loss of heterozygosis, allelic imbalance, microsatellite instability, post-transcriptional control and DNA methylation. These genetic and epigenetic characteristics are hypothesized to provide a deep understanding of CAFs and a perspective on their clinical significance.

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“…In B-ALLs, multiple miRs are known to be dysregulated [16], [17], but only a few miRs, including miR-196b [18], miR-124a [19] and miR-143 [20], have been shown to inhibit B-ALL growth. Although expression profiling studies can implicate miRs as biomarkers, it is often difficult to differentiate ‘passenger miRs’ from ‘driver miRs’ [21].…”

Section: Introductionmentioning

confidence: 99%

Regulation of RAB5C Is Important for the Growth Inhibitory Effects of MiR-509 in Human Precursor-B Acute Lymphoblastic Leukemia

et al. 2014

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MicroRNAs (miRs) regulate essentially all cellular processes, but few miRs are known to inhibit growth of precursor-B acute lymphoblastic leukemias (B-ALLs). We identified miR-509 via a human genome-wide gain-of-function screen for miRs that inhibit growth of the NALM6 human B-ALL cell line. MiR-509-mediated inhibition of NALM6 growth was confirmed by 3 independent assays. Enforced miR-509 expression inhibited 2 of 2 additional B-ALL cell lines tested, but not 3 non-B-ALL leukemia cell lines. MiR-509-transduced NALM6 cells had reduced numbers of actively proliferating cells and increased numbers of cells undergoing apoptosis. Using miR target prediction algorithms and a filtering strategy, RAB5C was predicted as a potentially relevant target of miR-509. Enforced miR-509 expression in NALM6 cells reduced RAB5C mRNA and protein levels, and RAB5C was demonstrated to be a direct target of miR-509. Knockdown of RAB5C in NALM6 cells recapitulated the growth inhibitory effects of miR-509. Co-expression of the RAB5C open reading frame without its 3′ untranslated region (3′UTR) blocked the growth-inhibitory effect mediated by miR-509. These findings establish RAB5C as a target of miR-509 and an important regulator of B-ALL cell growth with potential as a therapeutic target.

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Methylation-mediated repression of microRNA-143 enhances MLL–AF4 oncogene expression

Cited by 55 publications

References 32 publications

miR-139-5p controls translation in myeloid leukemia through EIF4G2

miR-139-5p controls translation in myeloid leukemia through EIF4G2

Genetic alterations and epigenetic alterations of cancer-associated fibroblasts

Regulation of RAB5C Is Important for the Growth Inhibitory Effects of MiR-509 in Human Precursor-B Acute Lymphoblastic Leukemia

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