Deep MicroRNA sequencing reveals downregulation of miR-29a in neuroblastoma central nervous system metastasis Journal Article

  

Authors:	Cheung, I. Y.; Farazi, T. A.; Ostrovnaya, I.; Xu, H.; Tran, H.; Mihailovic, A.; Tuschl, T.; Cheung, N. K. V.
Article Title:	Deep MicroRNA sequencing reveals downregulation of miR-29a in neuroblastoma central nervous system metastasis
Abstract:	Central nervous system (CNS) is an increasingly common site of isolated metastasis for patients with Stage 4 neuroblastoma. To explore the microRNA (miRNA) profile of this metastatic process, miRNA sequencing was performed to identify miRNA sequence families with differential expression between tumor pairs (pre-CNS primary and CNS metastasis) from 13 patients with Stage 4 neuroblastoma. Seven miRNA sequence families had distinct expression in CNS metastases when compared with their corresponding pre-CNS primaries. MiR-7 was upregulated (3.75-fold), and miR-21, miR-22, miR-29a, miR-143, miR-199a-1-3p, and miR-199a-1-5p were downregulated (3.5-6.1-fold), all confirmed by quantitative reverse transcription-PCR. MiR-29a, previously shown to be downregulated in a broad spectrum of solid tumors including neuroblastoma, had the most significant decrease in all 13 CNS metastases (P=0.001). Its known onco-targets CDC6, CDK6, and DNMT3A, as well as B7-H3, an inhibitory ligand for T cells, and natural killer cells, were found to have higher differential expression in these 13 CNS metastases when compared with their paired primaries. Additionally, miR-29a expression in primary tumors was significantly lower among patients who eventually relapsed in the CNS. Irrespective of the amplification status of MYCN, which is known to be associated with metastasis, pre-CNS primaries, and CNS metastases had significantly lower miR-29a expression than non-CNS primary tumors. Among MYCN amplified cell lines, those from CNS relapse also had lower miR-29a expression than non-CNS relapse. These findings raised the hypothesis that miR-29a could be a biomarker for neuroblastoma CNS metastasis, and its downregulation may play a pivotal role in CNS progression. © 2014 Wiley Periodicals, Inc.
Keywords:	clinical article; human tissue; unclassified drug; human cell; cancer recurrence; cancer staging; t lymphocyte; reverse transcription polymerase chain reaction; microrna; gene expression; neuroblastoma; natural killer cell; upregulation; tumor growth; central nervous system metastasis; microrna 29a; microrna 143; human; priority journal; article; microrna 199a 1 3p; mirna 199a 1 5p
Journal Title:	Genes Chromosomes and Cancer
Volume:	53
Issue:	10
ISSN:	1045-2257
Publisher:	Wiley Periodicals, Inc
Date Published:	2014-10-01
Start Page:	803
End Page:	814
Language:	English
DOI:	10.1002/gcc.22189
PROVIDER:	scopus
PUBMED:	24898736
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84905725508&partnerID=40&md5=21e681df963027833e4338ff7591c297
Notes:	Export Date: 2 September 2014 -- CODEN: GCCAE -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/57979