Journal
ONCOLOGY REPORTS
Volume 35, Issue 4, Pages 1916-1924Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2016.4571
Keywords
ovarian cancer stem cells; anisomycin; long non-coding RNA BACE1-AS
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Funding
- National Natural Science Foundation of China [81202811]
- China Postdoctoral Science Foundation [2014M550250, 2015T80455]
- Shanghai Municipal Health Bureau Fund [20124320]
- Key Discipline Construction Project of Pudong Health Bureau of Shanghai [WZx2014-03]
- Discipline Leader Project of Pudong Bureau of Shanghai [PWRd2014-02]
- Shanghai Pudong District Science and Technology Innovation Project [PKJ2015-Y52]
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Human ovarian cancer stem cells (OCSCs) are one of the main factors affecting ovarian cancer cell metastasis, recurrence, prognosis and tolerance to chemotherapy drugs. However, the mechanisms of OCSC proliferation and invasion are not clear. Recent studies suggest that anisomycin can inhibit the proliferative and invasive ability of various tumor cells by increasing the production of the toxic amyloid beta (A beta 1-42) peptides from the amyloid precursor protein (APP). We explored whether anisomycin could also suppress human OCSC proliferation and invasion. The CD44(+)/CD117(+) OCSCs were enriched from human clinical ovarian tumor tissues. OCSCs treated with anisomycin showed reduced proliferation compared to controls. Moreover, anisomycin significantly suppressed the invasive capacity of OCSCs in vitro, as indicated by cell migration assays. The mRNA expression levels of long non-coding RNA (lncRNA) beta-site APP cleaving enzyme 1 antisense strand (BACE1-AS) were significantly increased in anisomycin-treated OCSCs compared to controls. In addition, mRNA and protein levels of BACE1 and A beta 1-42 were increased in anisomycin-treated OCSCs compared to controls. We confirmed that anisomycin suppressed the growth of xenograft tumors formed by OCSCs in vivo. Finally, when expression of lncRNA BACE1-AS was silenced using siRNA, BACE1 expression was downregulated and the antiproliferative and anti-invasive effects of anisomycin were reduced. Overall, we identified lncRNA BACE1-AS as a novel target for anisomycin. Elevation of lncRNA BACE1-AS expression is a potential mechanism for suppressing human OCSC proliferation and invasion.
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