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Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor.


ABSTRACT:

Background

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with poor prognosis. Hypoxia-inducible factor 1 (HIF-1) plays a crucial role in the cellular response to hypoxia and regulates the expression of multiple genes involved in tumor progression in various cancers. However, the importance of the expression of HIF-1? in MPNSTs is unclear.

Methods

The expression of HIF-1? was examined immunohistochemically in 82 MPNST specimens. Cell culture assays of human MPNST cells under normoxic and hypoxic conditions were used to evaluate the impact of anti-HIF-1?-specific siRNA inhibition on cell survival. A screening kit was employed to identify small molecules that inhibited HIF-1?.

Results

The nuclear expression of HIF-1? was positive in 75.6% of MPNST samples (62/82 cases). Positivity for HIF-1? was a significant poor prognostic factor both in univariate (P = 0.048) and multivariate (P ? 0.0001) analyses. HIF-1? knockdown abrogated MPNST cell growth, inducing apoptosis. Finally, chetomin, an inhibitor of HIF-1?, effectively inhibited the growth of MPNST cells and induced their apoptosis.

Conclusion

Inhibition of HIF-1? signaling is a potential treatment option for MPNSTs.

SUBMITTER: Fukushima S 

PROVIDER: S-EPMC5448771 | biostudies-literature |

REPOSITORIES: biostudies-literature

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