Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression

Marino, Maria Teresa; Grilli, Andrea; Baricordi, Cristina; Manara, Maria Cristina; Ventura, Selena; Pinca, Rosa Simona; Bellenghi, Maria; Calvaruso, Marco; Mattia, Gianfranco; Donati, Davide María; Tripodo, Claudio; Picci, Piero; Ferrari, Stefano; Scotlandi, Katia

doi:10.1093/annonc/mdu249

Cited by 35 publications

(34 citation statements)

References 23 publications

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“…Our data were consistent with previous studies demonstrating that the over-expression of miR-34a reduced the expression of c-MET, CDK4/6, and CCND1/CCNE2 in in vitro lung cancer models [19,20]. A recent study revealed that the expression of miR-34a was inversely correlated with c-MET expression in human glioblastoma tissues [31], and it was also reported that an inverse correlation existed between the expression of miR-34a and CCND1 in human Ewing sarcoma tissues [32]. However, no previous studies have addressed the relationship between miR-34a and these target genes in NSCLC.…”

Section: Discussionsupporting

confidence: 92%

The expression of microRNA-34a is inversely correlated with c-MET and CDK6 and has a prognostic significance in lung adenocarcinoma patients

et al. 2015

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We aimed to establish whether the expression of microRNA-34a (miR-34a) is correlated with that of c-MET and G1 phase regulators such as cyclin dependent kinase (CDK) 4, CDK6, and cyclin D (CCND) 1 in non-small cell lung cancer (NSCLC), and whether a relationship exists between miR-34a expression and both clinicopathologic factors and recurrence-free survival (RFS). For 58 samples archived from NSCLC patients, we measured the expression of miR-34a and c-MET, CDK4/6, and CCND1 by quantitative RT-PCR and assessed the relationship between miR-34a expression, clinicopathological factors, and RFS. The expression of miR-34a was significantly lower in squamous cell tumors (P < 0.001) and in tumors associated with lymphatic invasion (P = 0.001). We found significant inverse correlations between miR-34a and c-MET (R = -0.316, P = 0.028) and CDK6 expression (R = -0.4582, P = 0.004). RFS were longer in adenocarcinoma patients with high miR-34a expression than in those with low miR-34a expression (55.6 vs. 21.6 months; P = 0.020). With univariate analysis, statistically significant prognostic factors for RFS in adenocarcinoma patients were miR-34a expression (Relative risk (RR), 8.14; P = 0.049), TNM stage (RR, 13.55; P = 0.001), LN metastasis (RR, 4.19; P = 0.043), and the presence of lymphatic invasion (RR, 7.05; P = 0.015). In multivariate analysis, only miR-34a was prognostic for RFS (RR, 11.5; P = 0.027). miR-34a expression was inversely correlated with that of c-MET and CDK6 in NSCLC, and had prognostic significance for RFS, especially in adenocarcinoma patients.

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Section: Discussionsupporting

confidence: 92%

The expression of microRNA-34a is inversely correlated with c-MET and CDK6 and has a prognostic significance in lung adenocarcinoma patients

et al. 2015

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“…These data highlight the importance of investigating posttranscriptional mechanisms, including noncoding RNAs and RNAbinding proteins (RBPs), involved in gene expression regulation. Although noncoding RNAs have been found to be differentially expressed in Ewing sarcoma samples (9)(10)(11), and prognostic value has been established for some of them (12), the role of RBPs has been barely explored in Ewing sarcoma.…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 is a Novel Post-Transcriptional Regulator of Ewing Sarcoma Malignancy

Mancarella

Pasello

Ventura

et al. 2018

Clinical Cancer Research

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Large-scale sequencing studies have indicated that besides genomic alterations, the posttranscriptional regulation of gene expression or epigenetic mechanisms largely influences the clinical behavior of Ewing sarcoma. We investigated the significance of the RNA-binding protein IGF2BP3 in the regulation of Ewing sarcoma aggressiveness. Explorative study was performed in 14 patients with localized Ewing sarcoma using RNA sequencing. Next, 128 patients with localized Ewing sarcoma were divided into two cohorts. In the training set, 29 Ewing sarcoma samples were analyzed using Affymetrix GeneChip arrays. In the validation set, 99 Ewing sarcoma samples were examined using qRT-PCR. Patient-derived cell lines and experimental models were used for functional studies.Univariate and multivariate analyses indicated as a potent indicator of poor prognosis. Furthermore, mRNA was identified as a novel partner of IGF2BP3. Functional studies indicated IGF2BP3 as an oncogenic driver and mRNA as a sponge that by binding IGF2BP3, partly repressed its functions. The combined evaluation of and could identify different patient outcomes-high and low levels indicated poor survival (25%), whereas low and high levels indicated favorable survival (85.5%). The bromodomain and extraterminal domain inhibitor (BETi) JQ1 decreased IGF2BP3 expression, modified the expression of its validated targets and inhibited the capability of Ewing sarcoma cells to grow under anchorage-independent conditions. The combined assessment of and predicts recurrence in Ewing sarcoma patients. Thus, for patients with high expression of IGF2BP3 and poor probability of survival, the use of BETis should be clinically evaluated. .

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“…Overexpression of miR-34a reportedly suppresses tumor progression and leads to improved prognoses, whereas reduced miR-34a expression is associated with poor overall survival in several cancers [11–17]. The association between miR-34a levels and glioma has been more ambiguous.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-34a expression levels in serum and intratumoral tissue can predict bone metastasis in patients with hepatocellular carcinoma

et al. 2016

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Hepatocellular carcinoma (HCC) patients with bone metastasis (BM) suffer from pain and other symptoms that significantly reduce their quality of life. We screened a microRNA (miRNA) microarray to identify potential serum biomarkers for BM in HCC patients. A miRNA microarray was used to screen for BM-related miRNAs in paired serum samples from HCC patients with BM and from HCC patients without BM. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to quantify candidate miRNAs in serum samples from 106 independent HCC patients. Levels of candidate miRNAs in tissue samples from an independent cohort of 296 HCC patients were evaluated by in situ hybridization and intratumoral tissue microarray. The migration and invasion capabilities of HCCLM3 and SMMC-7721 cells were evaluated following treatment with a mimic and an inhibitor of miR-34a. Ninety miRNAs were differentially expressed in sera from HCC patients with BM when compared with sera from non-BM HCC patients (P < 0.05). Only miR-34a and miR-498 had false discovery rates (FDRs) < 0.05. In cohorts of 106 and 296 HCC patients, we found that reduced serum and intratumoral miR-34a expression levels were independent risk factors for developing BM. Migration and invasion experiments indicated that a reverse correlation existed between miR-34a and HCC tumor migration and invasion. This study demonstrates the potential for the use of miR-34a as a serum and intratumoral tissue biomarker for predicting the risk of BM in HCC patients.

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Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression

Abstract: By demonstrating its relationship with clinical outcome, we propose evaluation of miR-34a at diagnosis of EWS patients to allow early risk stratification. Validation of these results would nonetheless ultimately need a prospective assessment.

Cited by 35 publications

References 23 publications

The expression of microRNA-34a is inversely correlated with c-MET and CDK6 and has a prognostic significance in lung adenocarcinoma patients

The expression of microRNA-34a is inversely correlated with c-MET and CDK6 and has a prognostic significance in lung adenocarcinoma patients

Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 is a Novel Post-Transcriptional Regulator of Ewing Sarcoma Malignancy

MicroRNA-34a expression levels in serum and intratumoral tissue can predict bone metastasis in patients with hepatocellular carcinoma

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