Title

Mirna-337-3P Suppresses Neuroblastoma Progression By Repressing The Transcription Of Matrix Metalloproteinase 14

Keywords

Matrix metalloproteinase 14; MicroRNA-337-3p; Neuroblastoma; Transcriptional repression

Abstract

Recent evidence shows the emerging roles of endogenous microRNAs (miRNAs) in repressing gene transcription. However, the miRNAs inhibiting the transcription of matrix metalloproteinase 14 (MMP-14), a membrane-anchored MMP crucial for the tumorigenesis and aggressiveness, still remain largely unknown. In this study, through mining computational algorithm program and genome-wide Argonaute profiling dataset, we identified one binding site of miRNA-337-3p (miR-337-3p) within the MMP-14 promoter. We demonstrated that miR-337-3p was under-expressed and inversely correlated with MMP-14 expression in clinical specimens and cell lines of neuroblastoma (NB), the most common extracranial solid tumor in childhood. Patients with high miR-337-3p expression had greater survival probability. miR-337-3p suppressed the promoter activity, nascent transcription, and expression of MMP-14, resulting in decreased levels of vascular endothelial growth factor, in cultured NB cell lines. Mechanistically, miR-337-3p recognized its binding site and recruited Argonaute 2 to facilitate the enrichment of repressive epigenetic markers and decrease the binding of RNA polymerase II and specificity protein 1 on the MMP-14 promoter. Gain- and loss-of-function studies demonstrated that miR-337-3p suppressed the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo. In addition, restoration of MMP-14 expression rescued the NB cells from changes in these biological features. Taken together, these data indicate that miR-337-3p directly binds the MMP-14 promoter to repress its transcription, thus suppressing the progression of NB.

Publication Date

1-1-2015

Publication Title

Oncotarget

Volume

6

Issue

26

Number of Pages

22452-22466

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.18632/oncotarget.4311

Socpus ID

84941253824 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84941253824

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