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

Citation data:

PloS one, ISSN: 1932-6203, Vol: 12, Issue: 5, Page: e0177661

Publication Year:
2017
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Repository URL:
https://digitalcommons.dartmouth.edu/facoa/218
PMID:
28493990
DOI:
10.1371/journal.pone.0177661; 10.1371/journal.pone.0177661.g004; 10.1371/journal.pone.0177661.g008; 10.1371/journal.pone.0177661.g003; 10.1371/journal.pone.0177661.g001; 10.1371/journal.pone.0177661.g007; 10.1371/journal.pone.0177661.g002; 10.1371/journal.pone.0177661.g006; 10.1371/journal.pone.0177661.g005
Author(s):
James R. Howe; Emily S. Li; Sarah E. Streeter; Gilbert J. Rahme; Edmond Chipumuro; Grace B. Russo; Julia F. Litzky; L. Benjamin Hills; Kyla R. Rodgers; Patrick D. Skelton; Bryan W. Luikart; Wenhui Hu Show More Hide
Publisher(s):
Public Library of Science (PLoS); Figshare
Tags:
Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Life Sciences; Cell Biology; Genetics; Molecular Biology; Neuroscience; Cancer; Science Policy; 69999 Biological Sciences not elsewhere classified; glioblastoma proliferation neurogenesis; glioblastoma cell lines; mir -338-3p; dentate gyrus; mir -338-3p expression; mir -338-3p overexpression
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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.