miR-335 and miR-363 regulation of neuroblastoma tumorigenesis and metastasis.

Qiao J, Lee S, Paul P, Theiss L, Tiao J, Qiao L, Kong A, Chung DH
Surgery. 2013 154 (2): 226-33

PMID: 23806264 · PMCID: PMC4165591 · DOI:10.1016/j.surg.2013.04.005

BACKGROUND - microRNA (miRNA) functions broadly as post-transcriptional regulators of gene expression, and disproportionate miRNAs can result in dysregulation of oncogenes in cancer cells. We have previously shown that gastrin-releasing peptide receptor (GRP-R) signaling regulates tumorigenicity of neuroblastoma cells. Herein, we sought to characterize miRNA profile in GRP-R silenced neuroblastoma cells, and to determine the role of miRNAs on tumorigenicity and metastatic potential.

METHODS - Human neuroblastoma cell lines, BE(2)-C and SK-N-SH, were used for our study. Stably transfected GRP-R silenced cells were assessed for miRNA profiles. Cells were transfected with miR-335, miR-363, or miR-CON, a nontargeting control, and in vitro assays were performed. In vivo functions of miR-335 and miR-363 were also assessed in a spleen-liver metastasis murine model.

RESULTS - GRP-R silencing significantly increased expression of miR-335 and miR-363 in BE(2)-C cells. Overexpression of miR-335 and miR-363 decreased tumorigenicity as measured by clonogenicity, anchorage-independent growth, and metastasis determined by cell invasion assay and liver metastasis in vivo.

CONCLUSION - We report, for the first time, that GRP-R-mediated tumorigenicity and increased metastatic potential in neuroblastoma are regulated, in part, by miR-335 and miR-363. A better understanding of the anti-tumor functions of miRNAs could provide valuable insights to discerning molecular mechanisms responsible for neuroblastoma metastasis.

Copyright © 2013 Mosby, Inc. All rights reserved.

MeSH Terms (13)

ADAM Proteins Animals Cell Line, Tumor Cell Transformation, Neoplastic Humans Liver Neoplasms, Experimental Male Membrane Proteins Mice MicroRNAs Neoplasm Invasiveness Neuroblastoma Receptors, Bombesin

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