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Cited by 44MicroRNA in disease regulationCancer-related molecular mechanisms researchGlioma Diagnosis and Treatment

Functional profiling of precursor microRNAs identifies microRNAs essential for glioma proliferation

Open access
Haapa-Paananen, Saija, Chen, Ping, Hellström, Kirsi, Kohonen, Pekka, Hautaniemi, Sampsa, Kallioniemi, Olli, Perälä, Merja·2013·PLoS ONE
DOI 10.1371/journal.pone.0060930PMC PMC3618426
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Abstract

Cancer initiation and progression involve microRNAs that can function like tumor suppressors and oncogenes. The functional significance of most miRNAs is currently unknown. To determine systematically which microRNAs are essential for glioma growth, we screened a precursor microRNA library in three human glioblastoma and one astroglial cell line model systems. The most prominent and consistent cell proliferation-reducing hits were validated in secondary screening with an additional apoptosis endpoint. The functional screening data were integrated in the miRNA expression data to find underexpressed true functional tumor suppressor miRNAs. In addition, we used miRNA-target gene predictions and combined siRNA functional screening data to find the most probable miRNA-target gene pairs with a similar functional effect on proliferation. Nine novel functional miRNAs (hsa-miR-129, -136, -145, -155, -181b, -342-5p, -342-3p, -376a/b) in GBM cell lines were validated for their importance in glioma cell growth, and similar effects for six target genes (ROCK1, RHOA, MET, CSF1R, EIF2AK1, FGF7) of these miRNAs were shown functionally. The clinical significance of the functional hits was validated in miRNA expression data from the TCGA glioblastoma multiforme (GBM) tumor cohort. Five tumor suppressor miRNAs (hsa-miR-136, -145, -342, -129, -376a) showed significant underexpression in clinical GBM tumor samples from the TCGA GBM cohort further supporting the role of these miRNAs in vivo. Most importantly, higher hsa-miR-145 expression in GBM tumors yielded significantly better survival (p<0.005) in a subset of patients thus validating it as a genuine tumor suppressor miRNA. This systematic functional profiling provides important new knowledge about functionally relevant miRNAs in GBM biology and may offer new targets for treating glioma.

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Cited by

Sorted by citations

Authors
Haapa-Paananen, S., Chen, P., Hellström, K., Kohonen, P., Hautaniemi, S., Kallioniemi, O., & Perälä, M.
Affiliations
  • VTT Technical Research Centre of Finland (FI)
  • University of Helsinki (FI)
Corresponding author
Haapa-Paananen, Saija
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-04-05
Volume
8
Issue
4
Pages
e60930
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0060930
PMC
PMC3618426
OpenAlex
W2073703919
Cited by
44
References
1
Citations by year
2026: 1 · 2023: 1 · 2022: 2 · 2020: 1 · 2019: 6 · 2018: 1 · 2017: 6 · 2016: 6 · 2015: 8 · 2014: 11 · 2013: 1
FWCI
3.05
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
Academy of Finland
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
Keywords
microRNA, glioblastoma, glioma proliferation, tumor suppressor microRNA, ROCK1, RhoA, MET, CSF1R, FGF7, patient survival
MeSH terms
Glioblastoma, Humans, Neoplastic Cells, Circulating, Gene Expression Profiling, MicroRNAs, Cell Proliferation

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