miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating fas expression

Gangxiong Huang, Kazumasa Nishimoto, Zhichao Zhou, Dennis Hughes, Eugenie S. Kleinerman

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

The ability of osteosarcoma cells to form lung metastases has been inversely correlated to cell surface Fas expression. Downregulation of Fas allows osteosarcoma cells to circumvent FasL-mediated apoptosis upon entrance into the FasL + lung microenvironment. However, the mechanism of Fas regulation remains unclear. Here, we show that miRNA plays a role in the downregulation of Fas expression in osteosarcoma. Expression levels of several members of the miR-17-92 cluster including miR-20a and miR-19a were found to be higher in metastatic low-Fas-expressing LM7 cells than in the parental nonmetastatic high-Fas-expressing SAOS-2 cells. We also found an inverse correlation between Fas and miR-20a expression in all 8 cell lines derived from patient samples. Overexpression of miR-20a consistently resulted in the downregulation of Fas expression in SAOS-2 cells and thus in decreased sensitivity to FasL. Conversely, inhibiting miR-20a in LM7 cells increased Fas expression and their sensitivity to FasL. Mice injected with LM7 stably transfected with anti-miR-20a had fewer metastases than those with control plasmids. Taken together, our findings suggest that miR-20a, encoded by miR-17-92, downregulates Fas expression in osteosarcoma, thus contributing to the metastatic potential of osteosarcoma cells by altering the phenotype and allowing survival in the FasL + lung microenvironment.

Original languageEnglish
Pages (from-to)908-916
Number of pages9
JournalCancer Research
Volume72
Issue number4
DOIs
Publication statusPublished - 2012 Feb 15
Externally publishedYes

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Osteosarcoma
Down-Regulation
Lung
Neoplasm Metastasis
MicroRNAs
Plasmids
Apoptosis
Phenotype
Cell Line
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating fas expression. / Huang, Gangxiong; Nishimoto, Kazumasa; Zhou, Zhichao; Hughes, Dennis; Kleinerman, Eugenie S.

In: Cancer Research, Vol. 72, No. 4, 15.02.2012, p. 908-916.

Research output: Contribution to journalArticle

Huang, Gangxiong ; Nishimoto, Kazumasa ; Zhou, Zhichao ; Hughes, Dennis ; Kleinerman, Eugenie S. / miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating fas expression. In: Cancer Research. 2012 ; Vol. 72, No. 4. pp. 908-916.
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