Downregulation of Foxo3 and TRIM31 by miR-551b in side population promotes cell proliferation, invasion, and drug resistance of ovarian cancer.
Downregulation of Foxo3 and TRIM31 by miR-551b in side population promotes cell proliferation, invasion, and drug resistance of ovarian cancer.
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侧群中miR-551b下调Foxo3和TRIM31促进卵巢癌细胞增殖、侵袭和耐药。
DOI：
10.1007/s12032-016-0842-9
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Yu X
中科院分区：
文献类型：
--
作者：
Wei Z;Liu Y;Wang Y;Zhang Y;Luo Q;Man X;Wei F;Yu X
卵巢癌（OVCa）干细胞与肿瘤生长、转移和复发相关，这是大多数OVCa相关死亡率背后的驱动力。这种癌细胞亚群的特点是不受控制的增殖、高侵袭性和对目前铂基治疗的耐药性。因此，靶向OVCa癌症干细胞已成为近期治疗发展的重点。然而，由于缺乏敏感和特异性的标记物，癌症干细胞的分离和纯化具有挑战性。在这项研究中，我们通过使用定量PCR阵列证明miR-551b在OVCa干细胞中上调，与这种恶性肿瘤的病理分级相关。体外实验表明，miR-551b促进OVCa细胞和肿瘤干细胞的增殖、侵袭和化疗耐药。进一步分析表明，miR-551b通过抑制Foxo3和TRIM31这两种重要的肿瘤抑制因子发挥作用。为了支持这一点，我们使用小鼠异种移植模型进行的体内实验显示，抑制miR-551b可显著增加OVCa细胞对顺铂的敏感性，延长宿主小鼠的存活时间。总之，我们的研究提示miR-551b可能是OVCa干细胞的潜在生物标志物，并探索其功能机制，为未来药物开发提供潜在的治疗靶点。本文的在线版本（doi:10.1007/s12032-016-0842-9）包含补充材料，仅供授权用户使用。
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. The online version of this article (doi:10.1007/s12032-016-0842-9) contains supplementary material, which is available to authorized users.
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DOI：
10.1038/nrclinonc.2013.5
发表时间：
2013-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
Nature reviews. Cancer
影响因子：
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影响因子：
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