MicroRNA and Target Protein Patterns Reveal Physiopathological Features of Glioma Subtypes

Abstract

Gliomas such as oligodendrogliomas (ODG) and glioblastomas (GBM) are brain tumours with different clinical outcomes. Histology-based classification of these tumour types is often difficult. Therefore the first aim of this study was to gain microRNA data that can be used as reliable signatures of oligodendrogliomas and glioblastomas. We investigated the levels of 282 microRNAs using membrane-array hybridisation and real-time PCR in ODG, GBM and control brain tissues. In comparison to these control tissues, 26 deregulated microRNAs were identified in tumours and the tissue levels of seven microRNAs (miR-21, miR-128, miR-132, miR-134, miR-155, miR-210 and miR-409-5p) appropriately discriminated oligodendrogliomas from glioblastomas. Genomic, epigenomic and host gene expression studies were conducted to investigate the mechanisms involved in these deregulations. Another aim of this study was to better understand glioma physiopathology looking for targets of deregulated microRNAs. We discovered that some targets of these microRNAs such as STAT3, PTBP1 or SIRT1 are differentially expressed in gliomas consistent with deregulation of microRNA expression. Moreover, MDH1, the target of several deregulated microRNAs, is repressed in glioblastomas, making an intramitochondrial-NAD reduction mediated by the mitochondrial aspartate-malate shuttle unlikely. Understanding the connections between microRNAs and bioenergetic pathways in gliomas may lead to identification of novel therapeutic targets.

Decreased miR-134 expression and its tumor-suppressive function in human osteosarcoma

“…Recently, miR-134 has been implicated in the pathogenesis of several types of tumors and plays dual roles in different tumors. It is significantly increased in head and neck squamous-cell carcinoma (HNSCC) and acts as a potential oncogene (Liu et al, 2014), while it is downregulated and acts as a candidate tumor suppressor in gastrointestinal stromal tumors (GISTs) (Haller et al, 2010), gliomas (Lages et al, 2011), non-small cell lung cancer (Li et al, 2012), hepatocellular carcinoma (Yin et al, 2013), and prostate cancer (Wang et al, 2011). However, very little is currently known about the links of miR-134 dysregulation to clinicopathological characteristics of osteosarcoma, and the functional attributes of miR-134 associated with osteosarcoma progression remain elusive.…”

MicroRNAs as efficient biomarkers in high-grade gliomas

“…microRNA-21 shows overexpression in GBM and other gliomas in a grade-specific manner [4,7,31,34,41,59]. It affects the major cancer pathways: TGF-β, p53, and mitochondrial initiated apoptosis pathways.…”

Recent Approaches and Novel Therapeutic Targets in Human Glioma

“…A number of miRNA has been reported to be overexperessed in GBM (Conti et al, 2009). In a recent report, it has been found that seven miRNAs expression pattern (miR-21, miR-128, miR-132, miR-134, miR-155, miR-210 and miR-409) allows to discriminate between oligodendroglioma and glioblastoma (Conti et al, 2009;Ciafre et al, 2005;Lages et al, 2011). They are thought to play very important role in cell cycle control, cell proliferation, differentiation and apoptosis (EsquelaKerscher et al, 2006).…”