The human nucleophosmin 1 mutation A inhibits myeloid differentiation of leukemia cells by modulating miR-10b

Zou, Qin; Tan, Shi; Yang, Zailin; Wang, Juan; Xian, Jing; Zhang, Shuaishuai; Jin, Hongjun; Yang, Lu; Wang, Lu; Zhang, Ling

doi:10.18632/oncotarget.12216

Cited by 15 publications

(13 citation statements)

References 45 publications

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“…Our group and others found that KLF4 gene expression is silenced by promoter hypermethylation in B‐cell lymphomas and T‐ALL . In addition to CpG methylation, downregulation of KLF4 is associated with deregulation of microRNAs such as miR‐10a and miR‐10b, and the transcriptional repression of KLF4 by CDX2 in AML is associated with inhibition of PPARγ signaling . Conversely, when human CD34 + cells are transduced with ZMYM2‐FGFR, the fusion protein product of the t(8;13)(p11;q12) chromosomal translocation found in myeloproliferative neoplasm, and transplanted into NSG mice, the mice display elevated KLF4, suggesting a potential oncogenic function .…”

Section: Role Of Klf4 In Leukemic Stem Cellsmentioning

confidence: 93%

Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4

Park

Lewis

Chen

et al. 2019

Stem Cells Translational Medicine

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Pluripotent and tissue‐specific stem cells, such as blood‐forming stem cells, are maintained through a balance of quiescence, self‐renewal, and differentiation. Self‐renewal is a specialized cell division that generates daughter cells with the same features as the parental stem cell. Although many factors are involved in the regulation of self‐renewal, perhaps the most well‐known factors are members of the Krüppel‐like factor (KLF) family, especially KLF4, because of the landmark discovery that this protein is required to reprogram somatic cells into induced pluripotent stem cells. Because KLF4 regulates gene expression through transcriptional activation or repression via either DNA binding or protein‐to‐protein interactions, the outcome of KLF4‐mediated regulation largely depends on the cellular context, cell cycle regulation, chromatin structure, and the presence of oncogenic drivers. This study first summarizes the current understanding of the regulation of self‐renewal by KLF proteins in embryonic stem cells through a KLF circuitry and then delves into the potential function of KLF4 in normal hematopoietic stem cells and its emerging role in leukemia‐initiating cells from pediatric patients with T‐cell acute lymphoblastic leukemia via repression of the mitogen‐activated protein kinase 7 pathway. stem cells translational medicine 2019;8:568–574

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Section: Role Of Klf4 In Leukemic Stem Cellsmentioning

confidence: 93%

Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4

Park

Lewis

Chen

et al. 2019

Stem Cells Translational Medicine

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“…NPM1 is a multifunctional protein that controls cell growth and genome stability through a mechanism either involving nucleolar-cytoplasmic shuttling or a fine modulation of the whole BER pathway 11,19 . Recently, an important role for NPM1 in miRNA biology, associated with cancer development, was outlined [20][21][22] . Abnormal cytoplasmic APE1 and NPM1 levels were associated with the oncogenic progression and chemoresistance of HGSC (high-grade serous ovarian adenocarcinoma), a prediction of a poor prognosis therein 23,24 , and a dysregulation of the BER and miR-221/222 processing pathways in AML cells 18,25 .…”

mentioning

confidence: 99%

Architecture of The Human Ape1 Interactome Defines Novel Cancers Signatures

Ayyildiz

Antoniali

D’Ambrosio

et al. 2020

Sci Rep

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APE1 is essential in cancer cells due to its central role in the Base Excision Repair pathway of DNA lesions and in the transcriptional regulation of genes involved in tumor progression/chemoresistance. Indeed, APE1 overexpression correlates with chemoresistance in more aggressive cancers, and APE1 protein-protein interactions (PPIs) specifically modulate different protein functions in cancer cells. Although important, a detailed investigation on the nature and function of protein interactors regulating APE1 role in tumor progression and chemoresistance is still lacking. The present work was aimed at analyzing the APE1-PPI network with the goal of defining bad prognosis signatures through systematic bioinformatics analysis. By using a well-characterized HeLa cell model stably expressing a flagged APE1 form, which was subjected to extensive proteomics analyses for immunocaptured complexes from different subcellular compartments, we here demonstrate that APE1 is a central hub connecting different subnetworks largely composed of proteins belonging to cancer-associated communities and/or involved in RNA-and DNA-metabolism. When we performed survival analysis in real cancer datasets, we observed that more than 80% of these APE1-PPI network elements is associated with bad prognosis. Our findings, which are hypothesis generating, strongly support the possibility to infer APE1-interactomic signatures associated with bad prognosis of different cancers; they will be of general interest for the future definition of novel predictive disease biomarkers. Future studies will be needed to assess the function of APE1 in the protein complexes we discovered. Data are available via ProteomeXchange with identifier PXD013368.Alteration of DNA repair mechanisms is an important hallmark of cancer cells, and plays a role both in the onset of an initial cancerous phenotype and in tumor progression. Tumor cells can develop drug resistance through repair mechanisms that counteract the DNA damage induced by chemotherapy or radiotherapy 1,2 . Thus, specific DNA repair inhibitors are often combined with DNA-damaging agents to improve therapy efficacy. Emerging evidences in tumor biology suggest that: i) protein-protein interactions (PPIs) specifically modulate both canonical and non-canonical roles of DNA repair enzymes; ii) RNA processing pathways participate in DNA-Damage Response (DDR); iii) defects in the above-mentioned regulatory mechanisms are associated with cancer genomic instability 3 . Very recent studies clearly show that many DNA repair proteins are associated with those involved in RNA metabolism, proving a role of their interactome network in undertaking non-canonical functions affecting gene expression in tumors. In addition, novel studies have shown that interaction of DDR components and miRNA biogenesis process is linked to cancer development 2 . In the context of these emerging lines, we already demonstrated the crucial role that enzymes belonging to the base excision DNA repair (BER) pathway play 4 . In particular, we showe...

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“…miR-10b has been widely studied in cancer (29,30), angiogenesis (31) and embryonic development (32) by focusing on different targets. It has been found that miR-10b regulates myeloid differentiation and neuroblastoma cell differentiation (24,25). Okamoto et al found that miR-10b was significantly downregulated during osteoblast differentiation (26).…”

Section: Discussionmentioning

confidence: 99%

“…miR-10b has been suggested as a regulator for cell differentiation (24,25). A recent study has reported that miR-10b shows decreased expression during osteoblast differentiation (26).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR-10b promotes osteoblast differentiation through targeting Bcl6

Yang

Wang

et al. 2017

International Journal of Molecular Medicine

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MicroRNAs (miRNAs or miRs) have been shown to play a critical role in osteoblast differentiation. miR-10b has been found to be downregulated during osteoblast differentiation; however, its precise effect on osteoblast differentiation remains unknown. In this study, we aimed to investigate the potential role of miR-10b and the potential underlying mechanism in regulating osteoblast differentiation. We found that miR-10b was downregulated during osteoblast differentiation. Overexpression of miR-10b inhibited osteoblast differentiation, whereas the suppression of miR-10b promoted osteoblast differentiation. Bioinformatics analysis and the dual-luciferase reporter assay demonstrated that miR-10b could target the 3'-untranslated regions of B cell lymphoma 6 (Bcl6) which is an important regulator of osteoblast differentiation. Real‑time quantitative polymerase chain reaction and western blot analysis showed that miR-10b directly regulated Bcl6 expression. Further experiments showed that the overexpression of miR-10b increased the expression of signal transducer and activator of transcription 1 (STAT1) and blocked Runt-related transcription factor 2 (Runx2) nuclear translocation, whereas miR-10b suppression showed an opposite effect. Moreover, the miR-10b suppression-induced effects were partially reversed by Bcl6 knockdown. Taken together, our study suggests that miR-10b contributes to osteoblast differentiation through targeting Bcl6, providing a novel insight into understanding the molecular mechanism underlying osteoblast differentiation and suggesting a potential target for inhibiting bone loss.

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The human nucleophosmin 1 mutation A inhibits myeloid differentiation of leukemia cells by modulating miR-10b

Cited by 15 publications

References 45 publications

Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4

Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4

Architecture of The Human Ape1 Interactome Defines Novel Cancers Signatures

Downregulation of miR-10b promotes osteoblast differentiation through targeting Bcl6

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