Identification of dysregulated miRNAs and their regulatory signature in glioma patients using the partial least squares method

Shou, Jiajun; Gu, Shaohua; Gu, Wentao

doi:10.3892/etm.2014.2041

Cited by 14 publications

(16 citation statements)

References 29 publications

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“…were significantly increased in patient tumor samples and its high expression was associated with a reduction in survival time (11). Another study identified that the low expression of miR-1908 predicted a poor prognosis in glioma (12). In addition, miR-1908 has also been associated with the prognosis of chordoma, hepatoma and melanoma (13)(14)(15)(16).…”

Section: Discussionmentioning

confidence: 99%

Low expression of microRNA-1908 predicts a poor prognosis for patients with ovarian cancer

Teng

Zheng

2017

Oncology Letters

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Abstract. MicroRNAs (miRs) serve important roles in cancer genesis and progression. The expression of miR-1908 has been reported in a number of types of cancer; however, the clinical significance of miR-1908 in human ovarian cancer (OC) remains unclear. A total of 491 patients with OC from The Cancer Genome Atlas project cohort were selected and divided into two groups according to the median expression level of miR-1908. Univariate and multivariate analyses, using the Kaplan-Meier method and Cox regression, were performed to identify the characteristics that predict OC prognosis. Bioinformatics tools were used to identify potential targets of miR-1908. It was identified that the low expression of miR-1908 is associated with a poor prognosis for OC (P<0.05). The potential target genes of miR-1908 included podocan-like 1, JunB AP-1 transcription factor subunit, homeobox B8, SET binding factor 1 and sirtuin 2; high expression of these five genes additionally predicted a poor prognosis. These results suggest that miR-1908 may be a suitable target for the development of novel approaches in OC diagnosis and therapy in the future.

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Section: Discussionmentioning

confidence: 99%

Low expression of microRNA-1908 predicts a poor prognosis for patients with ovarian cancer

Teng

Zheng

2017

Oncology Letters

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“…This approach enabled the identification of miRNAs whose expression levels were significantly altered in tumor tissue compared to peripheral brain tissue of the same patient, including miR-221, which was strongly up-regulated in GBM, and a set of brain-enriched miRNAs (miR-128, miR-181a, miR-181b, and miR-181c), which were down-regulated in GBM [32]. Very recently, a number of prognostic miRNA signatures have been reported for GBM [33–35, 15, 36, 37, 18–20, 38, 39]. We compared these signatures with our signature in terms of complexity, independent validation, and the approach used for identification of the signature.…”

Section: Discussionmentioning

confidence: 99%

“…For data sets with moderate dimensionality such as miRNA microarray data sets with typically a few hundreds of miRNAs expressed, the number of features contained in a signature should be of low complexity and in the range of smaller than 10. From the above cited studies, only five extracted a miRNA signature with low complexity that have been subsequently validated in an independent cohort [15, 37, 18–20]. Cheng et al [15] focused on MGMT promoter methylation positive tumors only and defined a 5-miRNA signature that was validated in an appropriate subset of the so-called Chinese Glioma Genome Atlas.…”

Section: Discussionmentioning

confidence: 99%

“…The small-noncoding RNAs described in Manterola et al [18] allow molecular diagnosis of GBM using blood serum samples but the authors did not show usability with regard to outcome prediction whilst our signature was particularly developed for the purpose of predicting survival outcome. In a study by Shou et al [20] three miRNAs were presented that statistically significantly allow differentiation into groups of patients with favorable and unfavorable prognosis. However, this approach was limited to separate and univariate analysis for each of the three miRNAs and the study did not include an independent validation of the results.…”

Section: Discussionmentioning

confidence: 99%

“…With a high degree of promiscuity miRNAs target and regulate several mRNA species encoding for proteins involved in various signaling pathways [14]. Accumulating evidence indicates that miRNA expression signatures can serve as biomarkers for diagnosis and risk assessment of diverse malignancies, including GBM [15–20]. Given that the available prognostic markers can segregate GBM patients only to a limited extent, additional markers and/or signatures have to be defined.…”

Section: Introductionmentioning

confidence: 99%

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A 4-miRNA signature predicts the therapeutic outcome of glioblastoma

et al. 2016

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Multimodal therapy of glioblastoma (GBM) reveals inter-individual variability in terms of treatment outcome. Here, we examined whether a miRNA signature can be defined for the a priori identification of patients with particularly poor prognosis.FFPE sections from 36 GBM patients along with overall survival follow-up were collected retrospectively and subjected to miRNA signature identification from microarray data. A risk score based on the expression of the signature miRNAs and cox-proportional hazard coefficients was calculated for each patient followed by validation in a matched GBM subset of TCGA. Genes potentially regulated by the signature miRNAs were identified by a correlation approach followed by pathway analysis.A prognostic 4-miRNA signature, independent of MGMT promoter methylation, age, and sex, was identified and a risk score was assigned to each patient that allowed defining two groups significantly differing in prognosis (p-value: 0.0001, median survival: 10.6 months and 15.1 months, hazard ratio = 3.8). The signature was technically validated by qRT-PCR and independently validated in an age- and sex-matched subset of standard-of-care treated patients of the TCGA GBM cohort (n=58). Pathway analysis suggested tumorigenesis-associated processes such as immune response, extracellular matrix organization, axon guidance, signalling by NGF, GPCR and Wnt. Here, we describe the identification and independent validation of a 4-miRNA signature that allows stratification of GBM patients into different prognostic groups in combination with one defined threshold and set of coefficients that could be utilized as diagnostic tool to identify GBM patients for improved and/or alternative treatment approaches.

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eNOS expression and NO release during hypoxia is inhibited by miR-200b in human endothelial cells

et al. 2018

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The nitric oxide (NO) secreted by vascular endothelium is required for the maintenance of cardiovascular homeostasis. Diminished release of NO generated by endothelial NO synthase contributes to endothelial dysfunction. Hypoxia and ischemia reduce endothelial eNOS expression via posttranscriptional mechanisms that result in NOS3 transcript destabilization. Here, we examine whether microRNAs contribute to this mechanism. We followed the kinetics of hypoxia-induced changes in NOS3 mRNA and eNOS protein levels in primary human umbilical vein endothelial cells (HUVECs). Utilizing in silico predictive protocols to identify potential miRNAs that regulate eNOS expression, we identified miR-200b as a candidate. We established the functional miR-200b target sequence within the NOS3 3′UTR, and demonstrated that manipulation of the miRNA levels during hypoxia using miR-200b mimics and antagomirs regulates eNOS levels, and established that miR-200b physiologically limits eNOS expression during hypoxia. Furthermore, we demonstrated that the specific ablation of the hypoxic induction of miR-200b in HUVECs restored eNOS-driven hypoxic NO release to the normoxic levels. To determine whether miR-200b might be the only miRNA that had this effect, we utilized Next Generation Sequencing (NGS) to follow hypoxia-induced changes in the miRNA levels in HUVECS and found 83 novel hypoxamiRs, with two candidate miRNAs besides miR-200b that could potentially influence eNOS levels. Taken together, the data establish miR-200b-eNOS regulation as a first hypoxamiR-based mechanism that limits NO bioavailability during hypoxia in endothelial cells, and show that hypoxamiRs could become useful therapeutic targets for cardiovascular diseases and other hypoxic-related diseases including various types of cancer.Electronic supplementary materialThe online version of this article (10.1007/s10456-018-9620-y) contains supplementary material, which is available to authorized users.

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Identification of dysregulated miRNAs and their regulatory signature in glioma patients using the partial least squares method

Cited by 14 publications

References 29 publications

Low expression of microRNA-1908 predicts a poor prognosis for patients with ovarian cancer

Low expression of microRNA-1908 predicts a poor prognosis for patients with ovarian cancer

A 4-miRNA signature predicts the therapeutic outcome of glioblastoma

eNOS expression and NO release during hypoxia is inhibited by miR-200b in human endothelial cells

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