Downregulation of Foxo3 and TRIM31 by miR-551b in side population promotes cell proliferation, invasion, and drug resistance of ovarian cancer

Ovarian cancer (OVCa) stem cells are associated with tumor growth, metastasis, and recurrence, which are driving forces behind a majority of the OVCa-related mortality. This subpopulation of cancer cells are characterized by uncontrolled proliferation, high invasiveness, and resistance against the current platinum-based therapy. Thus, targeting OVCa cancer stem cells has been focused in recent therapeutic development. Isolation and purification of cancer stem cells are, however, challenging for the lack of sensitive and specific markers. In this study, we demonstrated that miR-551b was upregulated in OVCa stem cells, by using a quantitative PCR array, correlating with the pathological grades of this malignancy. In vitro experiments indicated that miR-551b promoted the proliferation, invasion, and chemoresistance of OVCa cells and cancer stem cells. Further analysis suggested that miR-551b functioned through the suppression of Foxo3 and TRIM31, two important tumor suppressors. In support of this, our in vivo experiments using mouse xenograft models showed that inhibiting miR-551b significantly increased the susceptibility of OVCa cells to cisplatin and prolonged the survival of the host mice. In conclusion, our study suggested miR-551b as a potential biomarker for OVCa stem cells and explored its functional mechanism, providing a potential therapeutic target for future drug development.