MicroRNA-29a activates a multi-component growth and invasion program in glioblastoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Yun Zhao, Wei Huang, Tae-Min Kim, Yuchae Jung, Lata G. Menon, Hongyan Xing, Hongwei Li, Rona S. Carroll, Peter J. Park, Hong Wei Yang, Mark D. Johnson

ABSTRACT

BACKGROUND: Glioblastoma is a malignant brain tumor characterized by rapid growth, diffuse invasion and therapeutic resistance. We recently used microRNA expression profiles to subclassify glioblastoma into five genetically and clinically distinct subclasses, and showed that microRNAs both define and contribute to the phenotypes of these subclasses. Here we show that miR-29a activates a multi-faceted growth and invasion program that promotes glioblastoma aggressiveness. METHODS: microRNA expression profiles from 197 glioblastomas were analyzed to identify the candidate miRNAs that are correlated to glioblastoma aggressiveness. The candidate miRNA, miR-29a, was further studied in vitro and in vivo. RESULTS: Members of the miR-29 subfamily display increased expression in the two glioblastoma subclasses with the worst prognoses (astrocytic and neural). We observed that miR-29a is among the microRNAs that are most positively-correlated with PTEN copy number in glioblastoma, and that miR-29a promotes glioblastoma growth and invasion in part by targeting PTEN. In PTEN-deficient glioblastoma cells, however, miR-29a nevertheless activates AKT by downregulating the metastasis suppressor, EphB3. In addition, miR-29a robustly promotes invasion in PTEN-deficient glioblastoma cells by repressing translation of the Sox4 transcription factor, and this upregulates the invasion-promoting protein, HIC5. Indeed, we identified Sox4 as the most anti-correlated predicted target of miR-29a in glioblastoma. Importantly, inhibition of endogenous miR-29a decreases glioblastoma growth and invasion in vitro and in vivo, and increased miR-29a expression in glioblastoma specimens correlates with decreased patient survival. CONCLUSIONS: Taken together, these data identify miR-29a as a master regulator of glioblastoma growth and invasion. More... »

PAGES

36

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13046-019-1026-1

DOI

http://dx.doi.org/10.1186/s13046-019-1026-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111655953

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30683134


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