Global Profiling in Vestibular Schwannomas Shows Critical Deregulation of MicroRNAs and Upregulation in Those Included in Chromosomal Region 14q32

Torres‐Martín, Miguel; Lassaletta, Luis; Campos, José M. de; Isla, Alberto; Gavilán, Javiér; Pinto, Giovanny R.; Burbano, Rommel Rodrı́guez; Latif, Farida; Meléndez, Bárbara; Castresana, Javier S.; Rey, Juan A.

doi:10.1371/journal.pone.0065868

Cited by 33 publications

(37 citation statements)

References 64 publications

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“…Identification of new molecules involved in VS growth is of crucial importance to develop novel therapeutic strategies for this disease. Although Torres-Martin et al (2013) reported decreased expression of miR-1 in human VS tissues in 2013, its effect on VS cell growth and associated molecular mechanisms have not yet been described. In the present study, we confirmed the down-regulation of miR-1 in VS specimens, with this phenomenon being particularly noticeable in those isolated from large tumors.…”

Section: Discussionmentioning

confidence: 99%

miR-1 association with cell proliferation inhibition and apoptosis in vestibular schwannoma by targeting VEGFA

et al. 2016

Genet. Mol. Res.

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A growing body of research has demonstrated the tumor suppressive function of microRNA (miR)-1 in many cancers. Our study aimed to investigate its role in vestibular schwannoma (VS). We examined miR-1 expression in 95 VS specimens and 79 normal vestibular nerves using quantitative real-time polymerase chain reaction. Moreover, miR-1 mimics, miR-1 inhibitors, and negative control oligonucleotides were transfected into HEI-193 human VS cells to investigate the functional significance of miR-1 expression in this condition at a cellular level. Finally, the role of vascular endothelial growth factor A (VEGFA) in miR-1-mediated HEI-193 cell growth was confirmed. miR-1 levels were significantly reduced in VS specimens compared with normal vestibular nerve tissues (P < 0.001). In addition, low levels of miR-1 were associated with larger tumor volumes. In functional assays, miR-1 suppressed HEI-193 cell proliferation and colony formation, and enhanced apoptosis. VEGFA was verified as a target gene of miR-1, and VEGFA overexpression partially negated the effects of miR-1 on HEI-193 cells. These findings suggest that miR-1 suppresses VS growth by targeting VEGFA, and should be considered as a potential therapeutic target for treatment of this condition.

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Section: Discussionmentioning

confidence: 99%

miR-1 association with cell proliferation inhibition and apoptosis in vestibular schwannoma by targeting VEGFA

et al. 2016

Genet. Mol. Res.

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“…The RNA quality was assessed by formaldehyde agarose gel electrophoresis and quantified spectrophotometrically. The GeneChip miRNA 1.0 array (Affymetrix, Santa Clara, CA) with coverage of miRBase v.11 was used in this study according to a previously described method . Details are provided in the Supporting Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Identification of MicroRNA-214 as a negative regulator of colorectal cancer liver metastasis by way of regulation of fibroblast growth factor receptor 1 expression

et al. 2014

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The purpose of this study was to identify microRNAs (miRNAs) involved in the pathology of colorectal cancer (CRC) liver metastasis and investigate their underlying mechanisms. A total of 39 miRNAs were identified to be differentially expressed between 16 primary CRC tissues with liver metastases and 16 CRC tissues without liver metastases from 32 patients by Affymetric miRNA microarrays. A panel of eight miRNAs were confirmed to be significantly and differentially expressed between CRC tissues with and without liver metastases through quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis in the 32 patients. In a validated cohort of 99 CRC patients (44 with and 55 without liver metastases), only miR-214 was validated to be significantly downregulated in CRC with liver metastases, which was associated with an unfavorable prognosis. Ectopic expression of miR-214 suppressed proliferation, migration, and invasion in vitro, tumor growth and liver metastasis in an in vivo xenograft mouse model, whereas miR-214 knockdown promoted proliferation, migration, and invasion in CRC cell lines. Further studies indicated that fibroblast growth factor receptor 1 (FGFR1) was a potential target of miR-214. Restoring miR-214 expression in CRC cells decreased endogenous FGFR1 messenger RNA (mRNA) and protein levels. FGFR1 knockdown mimicked the tumor suppressive effect of miR-214 on CRC cells, while reintroduction of FGFR1 abolished the tumor suppressive effect of miR-214 on CRC cells. Moreover, miR-214 expression levels were inversely correlated with FGFR1 in CRC patients. Conclusion: Downregulation of miR-214 expression was correlated with increased FGFR1 expression levels, which may contribute to increased CRC liver metastasis. miR-214 may serve as a potential marker to predict survival, and the miR-214-FGFR1 axis may be a therapeutic target in CRC patients. (HEPATOLOGY 2014;60:598-609) M etastasis is a complex process that includes a series of steps in which tumor cells grow, detach from the primary tumor site, and migrate to a distant organ. In colorectal cancer (CRC), the liver is the most common site for distant metastasis, and liver metastasis is a common cause of cancer-related deaths in CRC patients. 1,2 Clinically, 25% of CRC patients present with synchronous liver metastases at diagnosis, while other advanced CRC patients develop metachronous liver metastases within Abbreviations: CRC, colorectal cancer; FGFR1, fibroblast growth factor receptor 1; IHC, immunohistochemistry; miRNA, microRNA; qPCR, quantitative polymerase chain reaction..From the

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“…These results suggest chr19_34670 as a tumor suppressor in VS. Other candidate miRNAs identified in our study have been previously documented with the indicated capabilities in various tumors. For instance, miR-183 was found to be decreased in melanomas and schwannomas compared with local normal tissues or normal nerves [25,27]. This indicates the reliability of high-throughput sequencing platform for proliferation phenotype analysis and the potential important role of miRNAs in VS cell proliferation.…”

Section: Discussionmentioning

confidence: 90%

“…For instance, overexpression of miR-21 promotes VS growth by downregulating PTEN [22]; miR-7 functions as a tumor suppressor by targeting the EGFR, Pak1 and Ack2 oncogenes; and let-7d (a let-7 family member) is upregulated in both schwannomas and meningiomas [23,24]. Furthermore, recently, evidence showed global upregulation of the 14q32 chromosomal site, which contains miRNAs associated with VS formation and/or maintenance [25]. However, no evidence of a functional role for miRNAs in CVS has been documented to date.…”

Section: Introductionmentioning

confidence: 99%

chr19_34670, a newly identified miRNA, represses rapid tumor growth of cystic vestibular schwannomas by targeting transforming growth factor α and inhibiting MAPK pathway

Huo¹,

Yan²,

Wang³

et al. 2018

Oncotarget

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Purpose: Cystic vestibular schwannoma (CVS) is an aggressive form of vestibular schwannoma (VS) with rapid growth and poor outcomes. The molecular basis of CVS remains unclear. In this study, we aimed to investigate whether microRNAs (miRNAs) contribute to the development of CVS. Methods: We identified miRNAs that were differentially expressed between CVS and solid VS (SVS) tissues using high-throughput sequencing and quantitative real-time PCR analysis. Gene targets of the identified miRNA were predicted by bioinformatics tools and validated by luciferase reporter analysis. The effects of the miRNA and its target genes on the proliferation of primary VS cells were examined using CCK-8, flow cytometry, colony formation assay, and western-blot. Results: We identified a novel miRNA, chr19_34670, downregulated in CVS compared to SVS. chr19_34670 directly targeted the 3' untranslated region of transforming growth factor α (TGFα) mRNA and suppressed its expression. TGFα overexpression motivated VS cell proliferation, while this effect could be attenuated by chr19_34670. We also found that chr19_34670 inhibited the function of key proteins in the MAPK pathway by suppressing phosphorylation of ERK and MEK. Conclusions: chr19_34670 suppresses the aggressive proliferation observed in CVS by inhibiting TGFα expression and phosphorylated proteins in the MAPK pathway.

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Global Profiling in Vestibular Schwannomas Shows Critical Deregulation of MicroRNAs and Upregulation in Those Included in Chromosomal Region 14q32

Cited by 33 publications

References 64 publications

miR-1 association with cell proliferation inhibition and apoptosis in vestibular schwannoma by targeting VEGFA

miR-1 association with cell proliferation inhibition and apoptosis in vestibular schwannoma by targeting VEGFA

Identification of MicroRNA-214 as a negative regulator of colorectal cancer liver metastasis by way of regulation of fibroblast growth factor receptor 1 expression

chr19_34670, a newly identified miRNA, represses rapid tumor growth of cystic vestibular schwannomas by targeting transforming growth factor α and inhibiting MAPK pathway

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