A predicted miR-27a-mediated network identifies a signature of glioma

Yang, Shuxu; Wang, Kun; Qian, Cong; Song, Zhengfei; Pu, Peiyu; Zhang, Anling; Wang, Wei; Niu, Huanjiang; Li, Xinwei; Qi, Xuchen; Zhu, Yinxin; Wang, Yirong

doi:10.3892/or.2012.1955

Cited by 15 publications

(11 citation statements)

References 39 publications

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“…It was found that overexpression of exogenous miR-27a significantly decreased SFRP1 mRNA and protein expression [22]. MiR-27a was shown to have multiple predicted targets, among which are many tumor suppressors [23]. We chose to focus on SFRP1 and Wnt/beta-catenin pathways because they are dysregulated in glioma and intensively researched in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

MiR-27a regulates Wnt/beta-catenin signaling through targeting SFRP1 in glioma

Wang

Xie²,

Xie³

et al. 2015

NeuroReport

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Glioma is one of the most common intracranial tumors, and the prognosis is poor, although more and more treatments are employed. Wnt/beta-catenin signaling has been reported to be associated with glioma. SFRP1 acts as an antagonist and inhibits Wnt signaling by binding to Wnt molecules. In the present study, we aimed to investigate miRNA-27a as an antineoplastic factor that inhibits the Wnt/beta-catenin pathway by binding to the SFRP1 3'-UTR in glioma in vitro. We first showed that the expression of miR-27a was elevated in both glioma samples and cell lines. Furthermore, downregulation of miR-27a induced growth inhibition, cycle arrest, and apoptosis, and suppressed invasion/migration in glioma cell lines. Quantitative real-time PCR, western blot, and luciferase assay analysis showed that SFRP1 is a direct target of miR-27a. Overexpression of SFRP1 inhibited the malignancy of glioma cell lines. Our investigation showed that downregulation of miR-27a suppressed beta-catenin/TCF-4 transcription activity by targeting SFRP1. Our findings identify a role for miR-27a in glioma cell viability, cycle, apoptosis, and invasion/migration after activation of Wnt/beta-catenin signaling through SFRP1.

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Section: Discussionmentioning

confidence: 99%

MiR-27a regulates Wnt/beta-catenin signaling through targeting SFRP1 in glioma

Wang

Xie²,

Xie³

et al. 2015

NeuroReport

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“…The aberrant expression of miR-27a has been found to be associated with a variety of diseases [20-22]. Moreover, Zhao et al showed that miR-27a is important in cell proliferation, apoptosis, and tumorigenesis [23]. Yang et al found that miR-27a affects the apoptotic signaling pathway in glioma initiation and progression [24].…”

Section: Introductionmentioning

confidence: 99%

MiR-27a Regulates Apoptosis in Nucleus Pulposus Cells by Targeting PI3K

et al. 2013

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The precise role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus pulposus (NP) cells and found that the expression of miR-27a was increased. The overexpression of miR-27a was further verified using real-time RT-PCR. Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by directly targeting their 3’-UTRs, and this inhibition was abolished by mutation of the miR-27a binding sites. Various cellular processes including cell growth, proliferation, migration and adhesion are regulated by activation of the PI3K/AKT signaling pathway, and nucleus pulposus cells are known to strongly express the phosphorylated survival protein AKT. Our results identify PI3K as a novel target of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of nucleus pulposus cells. This present study revealed that downregulated miR-27a might develop a novel intervention for IDD treatment through the prevention of apoptosis in Nucleus pulposus Cells.

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“…In this regard, the overexpression of miR-146a is also able to cause upregulation of CREB and Cx43 in this cell line, in which miR-146a was upregulated by PKA activation. Furthermore, β2-AR adrenoceptor signaling activation decreases the severity of the glioma as well as decreases the promotion of molecules, including miR-155 (24-27) and miR-27a (28,29) via its signaling pathway. PKA, activated by 6Bnz, acts as a suppressor of the astrocytoma signaling pathway and glioma while the Epac signaling pathway, activated by 8CPT acts as a modulator.…”

Section: Discussionmentioning

confidence: 99%

“…miR-27a is an oncogenic and multidrug resistant miRNA overexpressed in glioma, which promotes cell proliferation (28). This microRNA is predicted to be involved in glioma progression and initiation via different signaling pathways, including adherens junction, focal adhesion, the mitogen-activated protein kinase signaling pathway, the p53 signaling pathway and the apoptotic signaling pathway (29). miR-27a is upregulated by Epac activation, however, PKA activation downregulates its level, although Cln was not able to significantly alter its levels.…”

Section: Discussionmentioning

confidence: 99%

Regulation of connexin 43 and microRNA expression via β2-adrenoceptor signaling in 1321N1 astrocytoma cells

Khaksarian

Mostafavi

Soleimani

et al. 2015

Molecular Medicine Reports

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Abstract. Connexin 43 (Cx43) is the main gap junction protein in astrocytes and exerts the same effects on growth inhibition in astrocytoma and glioma as microRNA-146a (miR-146a) in glioma. β2-adrenergic receptor (AR) signaling modulates Cx43 expression in myocytes via components downstream of protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). However, it remains to be elucidated how expression of Cx43 is modulated in astrocytes. In the present study, 1321N1 astrocytoma cells were treated with β2-AR signaling agents in order to evaluate the expression of Cx43 and miRNAs. RNA and protein were extracted from the cells for use in reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The results revealed that clenbuterol increased miR-146a level and upregulated Cx43 expression via cAMP/PKA at the mRNA and protein level. Pre-inhibition of adenyl cyclase decreased expression of Cx43 and miR-146a. PKA activation and overexpression of miR-146a in A-1321N1 cells increased the expression of Cx43. β2-AR stimulation and 6Bnz, a PKA activator, suppressed oncomiRs miR-155 and miR-27a, while 8-(4-chlorophenylthio)-2'-O-methyl adenosine-3',5'-cyclic monophosphate, an Epac activator, increased their levels. The current findings demonstrated that β2-AR signaling has growth inhibitory effects via modulation of the cAMP/PKA pathway in A-1321N1 cells through increasing the expression level of Cx43 and miR-146a as well as decreasing miR-155 and miR-27a levels. Thus, stimulation of the β2-AR and PKA signaling pathway may be a useful approach for astrocytoma therapy.

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A predicted miR-27a-mediated network identifies a signature of glioma

Cited by 15 publications

References 39 publications

MiR-27a regulates Wnt/beta-catenin signaling through targeting SFRP1 in glioma

MiR-27a regulates Wnt/beta-catenin signaling through targeting SFRP1 in glioma

MiR-27a Regulates Apoptosis in Nucleus Pulposus Cells by Targeting PI3K

Regulation of connexin 43 and microRNA expression via β2-adrenoceptor signaling in 1321N1 astrocytoma cells

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