MiR-338-3p regulates neuronal maturation and suppresses glioblastoma proliferation

Document Type

Article

Publication Date

5-11-2017

Publication Title

PLoS One

Department

Geisel School of Medicine

Abstract

Neurogenesis is a highly-regulated process occurring in the dentate gyrus that has been linked to learning, memory, and antidepressant efficacy. MicroRNAs (miRNAs) have been previously shown to play an important role in the regulation of neuronal development and neurogenesis in the dentate gyrus via modulation of gene expression. However, this mode of regulation is both incompletely described in the literature thus far and highly multifactorial. In this study, we designed sensors and detected relative levels of expression of 10 different miRNAs and found miR-338-3p was most highly expressed in the dentate gyrus. Comparison of miR-338-3p expression with neuronal markers of maturity indicates miR-338-3p is expressed most highly in the mature neuron. We also designed a viral "sponge" to knock down in vivo expression of miR-338-3p. When miR-338-3p is knocked down, neurons sprout multiple primary dendrites that branch off of the soma in a disorganized manner, cellular proliferation is upregulated, and neoplasms form spontaneously in vivo. Additionally, miR-338-3p overexpression in glioblastoma cell lines slows their proliferation in vitro. Further, low miR-338-3p expression is associated with increased mortality and disease progression in patients with glioblastoma. These data identify miR-338-3p as a clinically relevant tumor suppressor in glioblastoma.

DOI

10.1371/journal.pone.0177661

Original Citation

Howe JR 6th, Li ES, Streeter SE, Rahme GJ, Chipumuro E, Russo GB, Litzky JF, Hills LB, Rodgers KR, Skelton PD, Luikart BW. MiR-338-3p regulates neuronal maturation and suppresses glioblastoma proliferation. PLoS One. 2017 May 11;12(5):e0177661. doi: 10.1371/journal.pone.0177661. PMID: 28493990; PMCID: PMC5426787.

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