<i>miR-17∼92</i> cooperates with <i>RB</i> pathway mutations to promote retinoblastoma

Conkrite, Karina L.; Sundby, Maggie; Mukai, Sonoyo; Thomson, J. Michael; Mu, David; Hammond, Scott M.; MacPherson, David

doi:10.1101/gad.17027411

Cited by 167 publications

(194 citation statements)

References 44 publications

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“…In the present study, we demonstrated a significant correlation between the miR-17-92 cluster level and the proliferation, invasion and migration of osteosarcoma cells: the expression of miR-17-92 cluster was higher in cells with higher proliferation, invasion and migration potential. The positive association of miR-17-92 cluster with cell proliferation, invasion and migration suggests that miR-17-92 cluster may be categorized as a "metastasis promotor gene" in osteosarcoma, which was in line with previous reports [22,33,34].…”

Section: Discussionsupporting

confidence: 80%

Upregulation of microRNA-17-92 cluster associates with tumor progression and prognosis in osteosarcoma

Li¹,

Yang²,

Tian³

et al. 2014

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MicroRNA -17-92 (miR-17-92) cluster has been demonstrated to play a crucial role in various human cancers. However, its effects in osteosarcoma have not yet been elucidated. The purpose of this study was to investigate the clinical significance of miR-17-92 cluster in osteosarcoma. MiR-17-92 cluster expression in osteosarcoma clinical samples and cell lines was detected by real-time quantitative RT-PCR. Then, the association of miR-17-92 cluster level with survival of osteosarcoma patients was performed by the Kaplan-Meier and Cox proportional regression analyses. Furthermore, the effects of miR-17-92 cluster on tumorigenicity of osteosarcoma cell lines were evaluated by in vitro assays. The relative expression of miR-17-92 cluster in osteosarcoma tissues was significantly higher than those in adjacent normal tissues (P=0.001). And there was a relationship between miR-17-92 cluster upregulation and advanced TNM stage of osteosarcoma patients (P=0.037). Moreover, higher miR-17-92 cluster expression clearly predicted poorer Recurrence-free survival (P<0.001) and Overall survival (P=0.002). In the multivariate analysis, high miR-17-92 cluster expression was an independent prognostic factor for Recurrence-free survival (P<0.001) and Overall survival (P=0.002). Furthermore, the cellular proliferation, invasion, and migration of osteosarcoma cell lines were significantly accelerated by miR-17-92 cluster plasmid in vitro assays. Our findings showed that miR-17-92 cluster could serve as a promising marker for tumor recurrence and survival of osteosarcoma patients. Moreover, miR-17-92 cluster has been identified as a promoter for tumorigenicity of osteosarcoma cells, thus it might be a critical targeted therapy strategy for osteosarcoma.

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Section: Discussionsupporting

confidence: 80%

Upregulation of microRNA-17-92 cluster associates with tumor progression and prognosis in osteosarcoma

Li¹,

Yang²,

Tian³

et al. 2014

neo

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“…ECs lacking the 17∼92 cluster grew more slowly, as measured by BrdU incorporation, consistent with the known function of the cluster in promoting cell growth via repression of E2F or PTEN (Fig. 3A) (2,4,9,(29)(30)(31). ECs lacking the miR-17∼92 cluster demonstrated augmented adhesion to either gelatin or fibronectin, complementing data showing that overexpression of the cluster reduces adhesion (Fig.…”

Section: Resultssupporting

confidence: 72%

Endothelial miR-17∼92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling

Landskroner-Eiger

Qiu

Perrotta

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The contribution of endothelial-derived miR-17∼92 to ischemiainduced arteriogenesis has not been investigated in an in vivo model. In the present study, we demonstrate a critical role for the endothelial-derived miR-17∼92 cluster in shaping physiological and ischemiatriggered arteriogenesis. Endothelial-specific deletion of miR-17∼92 results in an increase in collateral density limbs and hearts and in ischemic limbs compared with control mice, and consequently improves blood flow recovery. Individual cluster components positively or negatively regulate endothelial cell (EC) functions in vitro, and, remarkably, ECs lacking the cluster spontaneously form cords in a manner rescued by miR-17a, -18a, and -19a. Using both in vitro and in vivo analyses, we identified FZD4 and LRP6 as targets of miR-19a/b. Both of these targets were up-regulated in 17∼92 KO ECs compared with control ECs, and both were shown to be targeted by miR-19 using luciferase assays. We demonstrate that miR-19a negatively regulates FZD4, its coreceptor LRP6, and WNT signaling, and that antagonism of miR-19a/b in aged mice improves blood flow recovery after ischemia and reduces repression of these targets. Collectively, these data provide insights into miRNA regulation of arterialization and highlight the importance of vascular WNT signaling in maintaining arterial blood flow.endothelium | arteriogenesis | vascular | microRNA

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“…Conversely, inhibiting miR-17∼92 may provide clinical benefit in PKD by increasing the expression of PKD1, PKD2, and HNF-1β. miR-17∼92 is known to regulate other signaling pathways, such as mTOR and TGF-β pathways, which are also implicated in the pathogenesis of cyst growth (28,(40)(41)(42). Bioinformatics algorithms predict that members of the miR-17∼92 cluster target thousands of mRNAs for posttranscriptional silencing.…”

Section: Discussionmentioning

confidence: 99%

miR-17∼92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease

Patel¹,

Williams

Hajarnis

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

145

142

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Polycystic kidney disease (PKD), the most common genetic cause of chronic kidney failure, is characterized by the presence of numerous, progressively enlarging fluid-filled cysts in the renal parenchyma. The cysts arise from renal tubules and are lined by abnormally functioning and hyperproliferative epithelial cells. Despite recent progress, no Food and Drug Administration-approved therapy is available to retard cyst growth. MicroRNAs (miRNAs) are short noncoding RNAs that inhibit posttranscriptional gene expression. Dysregulated miRNA expression is observed in PKD, but whether miRNAs are directly involved in kidney cyst formation and growth is not known. Here, we show that miR-17∼92, an oncogenic miRNA cluster, is up-regulated in mouse models of PKD. Kidney-specific transgenic overexpression of miR-17∼92 produces kidney cysts in mice. Conversely, kidney-specific inactivation of miR-17∼92 in a mouse model of PKD retards kidney cyst growth, improves renal function, and prolongs survival. miR-17∼92 may mediate these effects by promoting proliferation and through posttranscriptional repression of PKD genes Pkd1, Pkd2, and hepatocyte nuclear factor-1β. These studies demonstrate a pathogenic role of miRNAs in mouse models of PKD and identify miR-17∼92 as a therapeutic target in PKD. Our results also provide a unique hypothesis for disease progression in PKD involving miRNAs and regulation of PKD gene dosage.cilia | kinesin family member 3A | autosomal dominant polycystic kidney disease P olycystic kidney disease (PKD) is among the most common monogenic human diseases (1, 2). PKD is characterized by the presence of numerous fluid-filled cysts in the renal parenchyma. The cysts arise from renal tubules and are lined by abnormally functioning epithelial cells. The cyst epithelial cells secrete excessive fluid and display high rates of proliferation, which results in cyst expansion. The expanding cysts compress the surrounding normal nephrons, which cause renal failure. Based on the mode of inheritance, PKD is classified into autosomal dominant PKD (ADPKD) and autosomal recessive PKD (ARPKD). ADPKD is caused by mutations of PKD1 or PKD2, which encode polycystin-1 and polycystin-2, respectively. ARPKD is caused by mutations of polycystic kidney and hepatic disease 1 (PKHD1) which encodes fibrocystin (1, 3). Polycystin-1, polycystin-2, and fibrocystin localize to the primary cilium, a sensory organelle present on the apical surface of most cells in the body. Abnormalities of the primary cilium are linked to the pathogenesis of many forms of cystic kidney diseases, including PKD (1, 4, 5). Despite recent advances, no Food and Drug Administration-approved therapy is available for PKD patients.MicroRNAs (miRNAs) are noncoding RNAs that constitute the endogenous RNA interference pathway. miRNAs are transcribed as primary miRNAs (pri-miRNAs), which are sequentially processed by the enzymes Drosha and Dicer to produce mature miRNAs (6). Watson-Crick base pairing between nucleotides 2-8 (seed sequence) at the 5′ end of the matur...

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miR-17∼92 cooperates with RB pathway mutations to promote retinoblastoma

Cited by 167 publications

References 44 publications

Upregulation of microRNA-17-92 cluster associates with tumor progression and prognosis in osteosarcoma

Upregulation of microRNA-17-92 cluster associates with tumor progression and prognosis in osteosarcoma

Endothelial miR-17∼92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling

miR-17∼92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease

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