Gliomas display a microRNA expression profile reminiscent of neural precursor cells

Abstract

Gliomas express many genes that play a role in neural precursor cells (NPCs), but no direct comparison between glioma and stem cell (SC) gene expression profiles has been performed. To investigate the similarities and differences between gliomas and SCs, we compared the microRNA (miRNA) expression signatures of glial tumors, embryonic SCs (ESCs), NPCs, and normal adult brains from both human and mouse tissues. We demonstrated that both human gliomas (regardless of their grade) and methylcholanthrene-induced mouse glioma shared an miRNA expression profile that is reminiscent of NPCs. About half of the miRNAs expressed in the shared profile clustered in seven genomic regions susceptible to genetic/epigenetic alterations in various cancers. These clusters comprised the miR17 family, mir183-182, and the SC-specific clusters mir367-302 and mir371-373, which are upregulated in gliomas, ESCs, and NPCs. The bipartite cluster of 7 + 46 miRNAs on chromosome 14q32.31, which might represent the largest tumor suppressor miRNA cluster, was downregulated in the shared expression profile. This study provides the first evidence for association between these clusters and gliomas. Despite the broad similarity in the miRNA expression profiles, 15 miRNAs showed disparate expression between SC and gliomas. Ten miRNAs belong to the 2 SC-specific clusters and the remaining (mir135b, mir141, mir205, mir200C, and mir301a) have been previously shown to associate with malignancies. Our finding showed that all gliomas displayed NPC-like miRNA signatures, which may have implications for studies of glioma origins. Furthermore, careful study of the 15 miRNAs that differ in expression between SCs and gliomas, particularly those 5 that are not SC-specific, may enhance our understanding of gliomagenesis.

MicroRNA-146a Inhibits Glioma Development by Targeting Notch1

“…miR-146a is unique in that it is significantly enriched in the human tissues of skin (melanoma), cervical, breast, pancreas and prostate cancers compared to the same noncancerous tissues (42,51,53). Similarly, miR-146a was also upregulated in human glioblastoma tissues and in both human and mouse primary glioma cell lines (32). In this regard, increased expression of miR-146a can be viewed as a biomarker for cancers.…”

“…1C). Among these miRNAs, miR-146a, miR-182, miR-183, and miR199a-3p are shown to be enriched in diverse cancers, whereas miR-127 and miR-140 are downregulated in gliomas (32,46). In contrast to the unchanged expression of miR-146b, miR146a was significantly induced by EGFR vIII alone or in combination with ablation of Pten (Fig.…”

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics

“…63 demonstrated that gliomas display neural precursor cell (NPC)‐like miRNA signatures. In a human glioma panel, 71 of the 180 miRNAs investigated had a distinct expression pattern which matched that of the embryonic stem cells and neural precursor cells.…”

The Role of microRNAs in Gliomas and Their Potential Applications for Diagnosis and Treatment

“…These clusters comprise the miR17 family, miR183-182, and the SC-specific clusters (miR367-302 and miR371-373), which are upregulated in gliomas. Because the massive cluster of 53 miRNAs on chromosome 14q32.31 is downregulated, it may represent the largest tumor suppressive miRNA cluster 20 . Some of these clusters, such as miR17-92, which is one of the three miRNA clusters related to the miR-17 family, reportedly have a pro-oncogenic roles in other type of cancers 21 .…”

“…We have recently shown that gliomas share miRNA expression profiles that are similar to neural precursor cells 20 . This result is in agreement with the finding that gliomas contain heterogeneous neoplastic cell populations that phenotypically resemble undifferentiated or immature glial cells.…”