MiR-126 Regulates the ERK Pathway via Targeting KRAS to Inhibit the Glioma Cell Proliferation and Invasion
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MiR-126 Regulates the ERK Pathway via Targeting KRAS to Inhibit the Glioma Cell Proliferation and Invasion Yang Li 1 & Yunqian Li 2 & Pengfei Ge 2 & Chengyuan Ma 2
Received: 29 October 2015 / Accepted: 17 December 2015 / Published online: 5 January 2016 # Springer Science+Business Media New York 2016
Abstract The activity of some constitutive contained in the extracellular signal-regulated kinase (ERK) pathway plays crucial roles in glioma cell growth and proliferation. Emerging studies have reported that microRNA (miRNA) could regulate the ERK signal pathway by directly targeting various oncogenes. This study enabled us to discover that the average miR126 expression was significantly decreased in glioblastoma tissues, and this significant decrease was related to high histopathological grades. Our experiment also demonstrated that the over-expression of miR-126 suppressed glioma cell proliferation and invasion in vitro. Kirsten rat sarcoma viral oncogene (KRAS) which is involved in ERK pathway was directly targeted by miR-126 in glioma through binding to two sites in the 3′ untranslated region (3′-UTR) of KRAS mRNA. Notably, the expression level of KRAS was positively correlated to the activity of ERK pathway and its downstream regulators (phosphorylation level of ERK (pERK) and c-Fos). Furthermore, the over-expression of KRAS expression vector without the 3′-UTR partially reverses the tumor-suppressive effects of miR-126. Moreover, the up-regulation of miR-126 contributes to the aberrant activation of the ERK signaling and inhibits cell proliferation and invasion through targeting KRAS. Therefore, it was suspected that miR-126 may be a potential therapeutic target for high-grade glioma.
* Chengyuan Ma [email protected]; [email protected]
1
Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
2
Department of Neurosurgery, The First Hospital of Jilin University, Xinmin Street 71, Changchun 130021, Jilin Province, China
Keywords Glioma . miR-126 . KRAS . ERK pathway . Proliferation . Invasion
Introduction Glioma is a kind of tumor that occurs in the spine or brain [1], and it accounts for almost 80 % of all malignant brain cancers [2]. Furthermore, glioma is a primary malignant brain tumor characterized by poor prognosis and the median survival time of the most common subtype (glioblastoma) is only 14 months [3]. As suggested by a large number of studies, the association between several pathogenic factors (self-reported asthma, allergy [4], prediagnostic serum IgE [5]) and glioma is still contentious. Glioblastoma-initiating cells can inhibit the proliferation of T cell and enhance the apoptosis of immune suppressive regulatory T cells [6]. As suggested by Adel et al., DNA repair genes ERCC1, ERCC2 (XPD), and XRCC1 were significantly associated with an increase in the risk of glioma, while MGMT and PARP1 polymorphisms appeared to be significantly associated with a reduced risk of glioma [7]. Researchers have reported that the activation of Ras/R
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