MicroRNA profiling of low-grade glial and glioneuronal tumors shows an independent role for cluster 14q32.31 member miR-487b

Abstract

Low-grade (WHO I–II) gliomas and glioneuronal tumors represent the most frequent primary tumors of the central nervous system in children. They often have a good prognosis following total resection, however they can create many neurological complications due to mass effect, and may be difficult to resect depending on anatomic location. MicroRNAs have been identified as molecular regulators of protein expression/translation that can repress multiple mRNAs concurrently through base pairing, and play an important role in cancer, including brain tumors. Using the NanoString digital counting system, we analyzed the expression levels of 800 microRNAs in nine low-grade glial and glioneuronal tumor types (n=45). A set of 61 of these microRNAs were differentially expressed in tumors compared to brain and several showed levels varying by tumor type. The expression differences were more accentuated in subependymal giant cell astrocytoma, compared with other groups, and demonstrated the highest degree of microRNA repression validated by RT-PCR, including miR-129-2-3p, miR-219-5p, miR-338-3p, miR-487b, miR-885-5p, and miR-323a-3p. Conversely, miR-4488 and miR-1246 were overexpressed in dysembryoplastic neuroepithelial tumors compared with brain and other tumors. The cluster 14q32.31 member miR-487b was variably under expressed in pediatric glioma lines compared to human neural stem cells. Overexpression of miR-487b in a pediatric glioma cell line (KNS42) using lentiviral vectors led to a decrease in colony formation in soft agar (30%)(p<0.05), and decreased expression of known predicted targets PROM1 and Nestin (but not WNT5A). miR-487b overexpression had no significant effect on cell growth, proliferation, sensitivity to temozolomide, migration or invasion. In summary, microRNA regulation appears to play a role in the biology of glial and glioneuronal tumor subtypes, a finding that deserves further investigation.

The miR‐139‐5p regulates proliferation of supratentorial paediatric low‐grade gliomas by targeting the PI3K/AKT/mTORC1 signalling

“…miR‐21 and members of the miR‐17‐92 cluster) or down‐regulation of microRNAs with reported oncosuppressive effects in various settings. The latter included miR‐218 , miR‐124 , miR‐487b and miR‐139‐5p .…”

“…Thus far, however, the research conducted on these noncoding RNA species in pLGGs has been largely descriptive. Moreover, the conclusions that can be drawn from these studies are frequently limited by the small number of cases analysed , the inclusion of high‐grade gliomas besides pLGGs or the inclusion of adult patients .…”

miR‐129 targets CDK1 and iASPP to modulate Burkitt lymphoma cell proliferation in a TAp63‐dependent manner

“…Among the predicted candidate miRNAs, miR‐129 serves as a biomarker and tumor suppressor in gastric cancer, breast cancer, and endometrial cancer . In addition, miR‐192 expression is abnormally downregulated in subependymal giant cell astrocytoma . Herein, we selected miR‐129 as an object for further experiments and speculated that miR‐129 might target CDK1 and iASPP to modulate TAp63‐mediated Burkitt lymphoma cells proliferation.…”

Cluster miRNAs and cancer: Diagnostic, prognostic and therapeutic opportunities

“…Gattolliat and colleagues in 2011 showed that miRNA cluster can be useful to differentiate the low‐risk neuroblastoma from high‐risk ones. The microarray and qRT‐PCR analysis showed the downregulation of members of 14q32.31 miRNA cluster in high risk group when compared with low risk neuroblastoma (Ames, Yuan, Vizcaíno, Yu, & Rodriguez, ). Thus, expression analysis of miR‐487b and miR‐410 could be useful for stratification of neuroblastoma into high‐risk and low‐risk types and relapse in favorable neuroblastoma (Gattolliat et al, ).…”