Altered Runx1 Subnuclear Targeting Enhances Myeloid Cell Proliferation and Blocks Differentiation by Activating a miR-24/MKP-7/MAPK Network

Zaidi, Sayyed K.; Dowdy, Christopher R.; Wijnen, André J. van; Lian, Jane B.; Raza, Azra; Stein, Janet L.; Croce, Carlo M.

doi:10.1158/0008-5472.can-09-1567

Cited by 100 publications

(100 citation statements)

References 43 publications

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“…miR-24 has been recently implicated in various biological processes Lal et al, 2009;Zaidi et al, 2009;Qin et al, 2010) and has been reported to be regulated by TGF-b (Sun et al, 2008) and bone morphogenetic protein 2 (BMP-2; Sun et al, 2009). Regulation by miRNAs provides a means for cells to prevent the accumulation of certain proteins by blocking protein translation.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of the two RhoA-specific GEF isoforms Net1/Net1A by TGF-β and miR-24: role in epithelial-to-mesenchymal transition

et al. 2011

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In the present study we analyzed the regulation of the two isoforms of the RhoA-specific guanine nucleotide exchange factor Net1 by transforming growth factor-b (TGF-b) in keratinocytes. We report that short-term TGF-b treatment selectively induced Net1 isoform2 (Net1A) but not Net1 isoform1. This led to upregulation of cytoplasmic Net1A protein levels that were necessary for TGF-b-mediated RhoA activation. Smad signaling and the MAPK/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway were involved in Net1A upregulation by TGF-b. Interestingly, long-term TGF-b treatment resulted in Net1 mRNA downregulation and Net1A protein degradation by the proteasome. Furthermore, we identified the microRNA miR-24 as a novel post-transcriptional regulator of Net1A expression. Silencing of Net1A resulted in disruption of E-cadherin-and zonula occludens-1 (ZO-1)-mediated junctions, as well as expression of the transcriptional repressor of E-cadherin, Slug and the mesenchymal markers N-cadherin, plasminogen activator inhibitor-1 (PAI-1) and fibronectin, indicating that late TGFb-induced downregulation of Net1A is involved in epithelial-to-mesenchymal transition (EMT). Finally, miR-24 was found to be implicated in the regulation of the EMT program in response to TGF-b and was shown to be directly involved in the TGF-b-induced breast cancer cell invasiveness through Net1A regulation. Our results emphasize the importance of Net1 isoform2 in the short-and long-term TGF-b-mediated regulation of EMT.

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Section: Discussionmentioning

confidence: 99%

Differential regulation of the two RhoA-specific GEF isoforms Net1/Net1A by TGF-β and miR-24: role in epithelial-to-mesenchymal transition

et al. 2011

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Section: Oncogenic Mirnasmentioning

confidence: 99%

“…35 Its upregulation is caused by binding of the AML-ETO fusion product to the miR-24-23-27 gene locus. 35 MiR-24 inhibits the synthesis of mitogen-activated protein kinase phosphatase 7, thereby facilitating cell growth through activation of c-jun and p38 kinases in myeloid leukemia cells. 35 MiR-125b and neighboring miRNA genes let-7c, miR-99a and miR-100 were aberrantly upregulated in TEL-AML1-positive ALL and different myeloid leukemias (Tables 1 and 2).…”

Section: Oncogenic Mirnasmentioning

confidence: 99%

“…35 MiR-24 inhibits the synthesis of mitogen-activated protein kinase phosphatase 7, thereby facilitating cell growth through activation of c-jun and p38 kinases in myeloid leukemia cells. 35 MiR-125b and neighboring miRNA genes let-7c, miR-99a and miR-100 were aberrantly upregulated in TEL-AML1-positive ALL and different myeloid leukemias (Tables 1 and 2). 24,46,47 Pro-B cells gained a survival advantage 24 and differentiation of CD34 þ myeloid progenitors was disturbed upon miR-125b overexpression.…”

Section: Oncogenic Mirnasmentioning

confidence: 99%

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MicroRNAs in acute leukemia: from biological players to clinical contributors

2011

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MicroRNAs (miRNAs) are involved in the management of hematopoiesis. As a consequence, miRNA dysregulation causes disruption of the hematopoietic system and leukemia may arise. We here comprehensively discuss miRNAs found discriminative for cytogenetic and molecular subtypes of acute leukemia. These miRNAs are either known miRNAs involved in leukemogenesis with proven tumor suppressor or oncogenic activities or are newly identified by high-throughput sequencing with yet unknown function. Furthermore, forces are outlined that drive aberrant miRNA function, which include genetic abnormalities (for example, deletions, translocations and mutations) and epigenetic aberrations (for example, aberrant DNA methylation or histone modifications). Interestingly, leukemia-silenced miRNAs can be re-expressed upon treatment with de-methylating agents. Targeting miRNA expression may serve a therapeutical role, albeit at present this way of targeted therapy is in its infancy. However, emerging knowledge about the biology of miRNAs in leukemia may result into a role for these miRNAs in the diagnosis and treatment of acute leukemia.

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“…While in other studies, it has been proved that miR-24 can inhibit the initial and progression of cancer cell [24,28,29]. Zaidi [40] reported that expression of miR-24 stimulated myeloid cell growth, rendered proliferation independent of interleukin-3 and blocked granulocytic differentiation. Qin [41] found that miR-24 regulates apoptosis by targeting FAF1 in cancer cells, which also suggested that miR-24 could be an effective drug target for treatment of hormone-insensitive prostate cancer or other types of cancers.…”

Section: Discussionmentioning

confidence: 98%

Clinical significance of microRNA-24 expression in esophageal squamous cell carcinoma

Dong¹,

B²,

Wang³

et al. 2015

neo

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microRNA-24 has been reported to participate in tumorgenesis and progression by several signaling pathways in various tumors. However, its potential as a serum diagnostic factor and predictive biomarker for esophageal squamous cell carcinoma (ESCC) has not been studied. in the present study, serum samples were collected from 105 pathologically proven ESCC patients and 30 healthy volunteers. All patients were treated with concurrent chemotherapy and radiotherapy. Real-time polymerase chain reaction was carried out to measure the serum miR-24 expression level in all patients and volunteers. The data were compared among radio-sensitive group (CR+PR, 62 patients), radio-resistant group (SD+PD, 43 patients) and healthy volunteers to elucidate the diagnostic value of serum miR-24 testing for ESCC and the predictive value of miR-24 expression of treatment response. in the result, of the 105 ESCC patients enrolled in the study, 62 patients achieved partial or complete response. The serum miR-24 level in ESCC patients is 4.82 times as high as that in healthy subjects(P<0.01), indicating that serum miR-24 expression could be an excellent diagnostic factor. The mean miR-24 serum levels differ by 2.05 folds between radiosensitive group and radioresistant group, indicating that it may serve as a biomarker for predicting the response of ESCC patient to CRT. Furthermore, the responsiveness of therapy is significantly correlated with Cyfra21-1(P<0.05), serum miR-24 level (P<0.05) and the myelosuppression (P<0.01). in the prsent study, we come to the conclusion that serum miR-24 has the potential to serve as a noninvasive biomarker for both ESCC diagnosis and predicting treatment responses to concurrent chemo-radiation therapy. ESCC patients with lower Cyfra21-1, higher miR-24, and severer myelosupression were much more sensitive to CRT. Key words: miR-24 expression, esophageal squamous cell carcinoma, chemo-radiation therapy, radiosensitivityEsophageal cancer (EC) is the sixth most common cancer and the fifth leading cause of cancer death in men worldwide, there was an estimated 482,300 new EC cases and 406,800 EC-caused deaths in 2008 worldwide [1]. Despite improved treatments in recent years, curative surgical resection, which is initially recommend for early stage cases, feasible for only 30-40% of patients [2]. While the outcome of surgery for patients with such an aggressive tumor has been unsatisfactory, with a 5-year survival rate less than 20% [3].Prognostic assessment is critical for making better therapeutic choices for ESCC patients, and the tumor-nodemetastasis (TNM) staging system is the key prognostic determinant. However, the variations in clinical responses to CRT are most evident for esophageal squamous cell carcinoma (ESCC), and the survival rates between responders and non-responders are quite different even in the same clinical stage [4,5]. Rapidly increasing findings on cancer biology provide prognostic information that complements and, in some cases, is more relevant than anatomical extent [6]. The discove...

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Altered Runx1 Subnuclear Targeting Enhances Myeloid Cell Proliferation and Blocks Differentiation by Activating a miR-24/MKP-7/MAPK Network

Cited by 100 publications

References 43 publications

Differential regulation of the two RhoA-specific GEF isoforms Net1/Net1A by TGF-β and miR-24: role in epithelial-to-mesenchymal transition

Differential regulation of the two RhoA-specific GEF isoforms Net1/Net1A by TGF-β and miR-24: role in epithelial-to-mesenchymal transition

MicroRNAs in acute leukemia: from biological players to clinical contributors

Clinical significance of microRNA-24 expression in esophageal squamous cell carcinoma

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