CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in Neuroblastoma.
CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in Neuroblastoma.
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CDC27-ODC1轴促进神经母细胞瘤的转移、加速铁死亡并预测不良预后
DOI：
10.3389/fonc.2022.774458
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发表时间：
2022
影响因子：
4.7
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Qiu L;Zhou R;Luo Z;Wu J;Jiang H
神经母细胞瘤 (NB) 是一种威胁儿童健康的毁灭性恶性肿瘤，MYCN 的扩增与治疗失败和不良预后相关。在这里，我们的目的是证明细胞分裂周期 27 (CDC27)（后期促进复合物的重要核心亚基）的作用及其在 NB 患者中的临床意义。在功能测定中，我们证明CDC27在体外和体内均促进NB细胞的细胞生长、转移和球体形成能力。为了进一步了解潜在机制，用 CDC27 siRNA 转染 SK-N-SH 细胞，并进行 RNA 测序。结果显示，CDC27 的下调导致 ODC1 的表达显着降低，ODC1 是 MYCN 的公认直接靶点。随后，我们进一步证明，ODC1的抑制显着减弱了CDC27对NB细胞增殖、转移和球体形成能力的促进作用，暗示CDC27至少部分以ODC1依赖性方式在NB中发挥其生物学行为。此外，CDC27使细胞更容易发生铁死亡，而ODC1的敲低则显着逆转了CDC27的促铁死亡作用。总的来说，我们的数据首次报道了 CDC27/ODC1 轴促进肿瘤发生，并作为 NB 铁死亡的正调节因子，强调 CDC27 可能代表神经母细胞瘤的一种新的治疗策略和预后生物标志物。
Neuroblastoma (NB) is a devastating malignancy threatening children’s health, and amplification of MYCN is associated with treatment failure and a poor outcome. Here, we aimed to demonstrate the role of cell division cycle 27 (CDC27), an important core subunit of the anaphase-promoting complex, and its clinical significance in NB patients. In functional assays, we illustrated that CDC27 promoted the cell growth, metastasis and sphere-formation ability of NB cells both in vitro and in vivo. To further understand the potential mechanism, SK-N-SH cells were transfected with CDC27 siRNA, and RNA-sequencing was performed. The results revealed that downregulation of CDC27 led to markedly reduced expression of ODC1, which is a well-established direct target of MYCN. Subsequently, we further illustrated that suppression of ODC1 significantly attenuated the promotion effect of CDC27 on the proliferation, metastasis, and sphere-formation ability of NB cells, hinting that CDC27 exerted its biological behavior in NB at least partly in an ODC1-dependent manner. In addition, CDC27 rendered cells more vulnerable to ferroptosis, while knockdown of ODC1 markedly reversed the pro-ferroptotic effect of CDC27. Collectively, our data is the first to report that the CDC27/ODC1 axis promotes tumorigenesis and acts as a positive regulator of ferroptosis in NB, highlighting that CDC27 may represent a novel therapeutic strategy and prognostic biomarker in neuroblastoma.
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影响因子：
9
作者：
Lu Y;Yang Q;Su Y;Ji Y;Li G;Yang X;Xu L;Lu Z;Dong J;Wu Y;Bei JX;Pan C;Gu X;Li B
通讯作者：
Li B
影响因子：
16.6
作者：
Litchfield, Kevin;Summersgill, Brenda;Yost, Shawn;Sultana, Razvan;Labreche, Karim;Dudakia, Darshna;Renwick, Anthony;Seal, Sheila;Al-Saadi, Reem;Broderick, Peter;Turner, Nicholas C.;Houlston, Richard S.;Huddart, Robert;Shipley, Janet;Turnbull, Clare
通讯作者：
Turnbull, Clare
DOI：
10.1158/1078-0432.ccr-08-3213
发表时间：
2009-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Evageliou NF;Hogarty MD
通讯作者：
Hogarty MD
影响因子：
4.6
作者：
Ignaternko, NA;Zhang, H;Gerner, EW
通讯作者：
Gerner, EW
影响因子：
64.8
作者：
AUVINEN, M;PAASINEN, A;HOLTTA, E
通讯作者：
HOLTTA, E