Department of ENT, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China

Nomura, Miyuki; Shiiba, Kenichi; Katagiri, Chiaki; Kasugai, Isao; Masuda, Kouhei; Sato, Iwao; Sato, Masayuki; Kakugawa, Yoichiro; Nomura, Eiki; Hayashi, Kenjiro; Nakamura, Yoshihiro; Nagata, Toshiyuki; Otsuka, T.; Katakura, Ryuichi; Yamashita, Yoshihisa; Sato, Masami; Tanuma, Nobuhiro; Shima, Hiroshi

doi:10.3892/or.2012.1862

Cited by 14 publications

(11 citation statements)

References 55 publications

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“…We explored the possibility that mir-17~92 increases ERK activation via suppression of dual-specificity phosphatases (DUSPs), which are well-known regulators of numerous MAPK family proteins, including ERK [57]. In particular, DUSP2, DUSP7 and DUSP10 suppress ERK activity and are demonstrated or predicted targets of mir-17~92 miRNAs [48, 58–60]. Interestingly, a recent publication linked miR-92 and DUSP10 to PDAC cell proliferation in vitro , suggesting that there may indeed be an important role for this regulatory axis in pancreatic tumorigenesis [61].…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs of themir-17~92cluster regulate multiple aspects of pancreatic tumor development and progression

et al. 2017

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by resistance to currently employed chemotherapeutic approaches. Members of the mir-17~92 cluster of microRNAs (miRNAs) are upregulated in PDAC, but the precise roles of these miRNAs in PDAC are unknown. Using genetically engineered mouse models, we show that loss of mir-17~92 reduces ERK pathway activation downstream of mutant KRAS and promotes the regression of KRASG12D-driven precursor pancreatic intraepithelial neoplasias (PanINs) and their replacement by normal exocrine tissue. In a PDAC model driven by concomitant KRASG12D expression and Trp53 heterozygosity, mir-17~92 deficiency extended the survival of mice that lacked distant metastasis. Moreover, mir-17~92-deficient PDAC cell lines display reduced invasion activity in transwell assays, form fewer invadopodia rosettes than mir-17~92-competent cell lines and are less able to degrade extracellular matrix. Specific inhibition of miR-19 family miRNAs with antagomirs recapitulates these phenotypes, suggesting that miR-19 family miRNAs are important mediators of PDAC cell invasion. Together these data demonstrate an oncogenic role for mir-17~92 at multiple stages of pancreatic tumorigenesis and progression; specifically, they link this miRNA cluster to ERK pathway activation and precursor lesion maintenance in vivo and identify a novel role for miR-19 family miRNAs in promoting cancer cell invasion.

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Section: Discussionmentioning

confidence: 99%

MicroRNAs of themir-17~92cluster regulate multiple aspects of pancreatic tumor development and progression

et al. 2017

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“…Dusp6 and Dusp10 acts as negative feedback regulators of ERK signalling [24,31]. Conversely, genes such as receptor tyrosine kinase KIT, its ligand stem cell factor (SCF) and KRAS, which induce ERK phosphorylation and promote cell proliferation [32], were upregulated by ascites.…”

Section: Discussionmentioning

confidence: 99%

Role of malignant ascites on human mesothelial cells and their gene expression profiles

et al. 2014

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BackgroundMalignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression.MethodsHuman OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays.ResultsAs compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P < 0.05, 484 genes were up-regulated and 165 genes were down-regulated in ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-κB survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated.ConclusionsThe results of this study not only provide evidence supporting the importance of the interplay between cancer cells and HPMCs but also define the role that the tumor environment plays in these interactions.

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“…We observed that expression of DUSP3 and DUSP10 was upregulated in AML. DUSP10 was reported to be up-regulated in colorectal cancer and kept Erk in cytosol by direct interaction, suggesting that DUSP10 also act as adaptor protein [21].…”

Section: Discussionmentioning

confidence: 99%

Deregulation of protein phosphatase expression in acute myeloid leukemia

2013

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Acute myeloid leukemia (AML) is a highly malignant disease of myeloid cell line. AML is the most frequent adult leukemia with inadequate treatment possibility. The protein phosphatases are critical regulators of cell signaling, and deregulation of protein phosphatases always contribute to cell transformation. Although many studies established a relationship between protein phosphatases and leukemia, little is known about the role of this group of proteins in AML. To address this issue, we initially identified the complete catalog of human protein phosphatase genes and used this catalog to study deregulation of protein phosphatases in AML. Using mRNA expression data of AML patients, we show that 11 protein phosphatases are deregulated in AML within 174 protein phosphatases. The GO enrichment study suggests that these genes are involved in multiple biological processes other than protein de-phosphorylation. Expression of DUSP10, PTPRC and PTPRE was significantly higher than average expression in AML, and a linear combination of DUSP10, MTMR11, PTPN4, and PTPRE expressions provides important information about disease subtypes. Our results provide an overview of protein phosphatase deregulation in AML.2

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Department of ENT, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China

Cited by 14 publications

References 55 publications

MicroRNAs of themir-17~92cluster regulate multiple aspects of pancreatic tumor development and progression

MicroRNAs of themir-17~92cluster regulate multiple aspects of pancreatic tumor development and progression

Role of malignant ascites on human mesothelial cells and their gene expression profiles

Deregulation of protein phosphatase expression in acute myeloid leukemia

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