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Int. J. Mol. Sci. 2018, 19(8), 2326; https://doi.org/10.3390/ijms19082326

Sonic Hedgehog Medulloblastoma Cancer Stem Cells Mirnome and Transcriptome Highlight Novel Functional Networks

1
Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy
2
Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy
3
Center for Life Nano Science@Sapienza, Istituto Itialiano di Tecnologia, 00161 Rome, Italy
4
Department of Radiological, Oncological and Pathological Science, Sapienza University, 00161 Rome, Italy
5
IRCCS Neuromed, Pozzilli, 86077 Isernia, Italy
6
Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children’s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy
These authors contributed equally to the manuscript.
*
Author to whom correspondence should be addressed.
Received: 23 June 2018 / Revised: 31 July 2018 / Accepted: 7 August 2018 / Published: 8 August 2018
(This article belongs to the Special Issue The Role of MicroRNAs in Human Diseases)
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Abstract

Molecular classification has improved the knowledge of medulloblastoma (MB), the most common malignant brain tumour in children, however current treatments cause severe side effects in patients. Cancer stem cells (CSCs) have been described in MB and represent a sub population characterised by self-renewal and the ability to generate tumour cells, thus representing the reservoir of the tumour. To investigate molecular pathways that characterise this sub population, we isolated CSCs from Sonic Hedgehog Medulloblastoma (SHH MB) arisen in Patched 1 (Ptch1) heterozygous mice, and performed miRNA- and mRNA-sequencing. Comparison of the miRNA-sequencing of SHH MB CSCs with that obtained from cerebellar Neural Stem Cells (NSCs), allowed us to obtain a SHH MB CSC miRNA differential signature. Pathway enrichment analysis in SHH MB CSCs mirnome and transcriptome was performed and revealed a series of enriched pathways. We focused on the putative targets of the SHH MB CSC miRNAs that were involved in the enriched pathways of interest, namely pathways in cancer, PI3k-Akt pathway and protein processing in endoplasmic reticulum pathway. In silico analysis was performed in SHH MB patients and identified several genes, whose expression was associated with worse overall survival of SHH MB patients. This study provides novel candidates whose functional role should be further investigated in SHH MB. View Full-Text
Keywords: microRNAs; cancer stem cells; medulloblastoma; Sonic Hedgehog pathway; RNA-sequencing microRNAs; cancer stem cells; medulloblastoma; Sonic Hedgehog pathway; RNA-sequencing
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Po, A.; Abballe, L.; Sabato, C.; Gianno, F.; Chiacchiarini, M.; Catanzaro, G.; De Smaele, E.; Giangaspero, F.; Ferretti, E.; Miele, E.; Besharat, Z.M. Sonic Hedgehog Medulloblastoma Cancer Stem Cells Mirnome and Transcriptome Highlight Novel Functional Networks. Int. J. Mol. Sci. 2018, 19, 2326.

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