Inhibition of Sirtuin 6 Induces Neuroblastoma Differentiation
Inhibition of Sirtuin 6 Induces Neuroblastoma Differentiation
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DOI：
10.21873/anticanres.12268
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发表时间：
2018-02-01
影响因子：
2
通讯作者：
Chung, Dai H.
中科院分区：
文献类型：
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作者：
Song, Ha Yong;Rellinger, Eric J.;Chung, Dai H.
背景/目的：去乙酰化酶 (SIRT) 在调节分化和增殖的各种信号通路中发挥着至关重要的作用。我们试图阐明 SIRT 在人神经母细胞瘤 (NB) 分化和增殖中的作用。材料和方法：用烟酰胺 (NAM)、一种非特异性 SIRT 抑制剂、SIRT 靶向短发夹 RNA 和视黄酸处理 NB 细胞，以评估细胞生长和分化。结果：SIRT 使用 NAM 参与 BE(2)-C 细胞的增殖和分化。具体来说，BE(2)-C 细胞中的 SIRT6 敲除减少了细胞增殖，诱导神经突延伸，与 p21(CIP1) 表达的诱导和 G1 细胞周期停滞相对应。 SIRT6 的强制重新过表达可以挽救这些效应。 SIRT6 表达在分化的人 NB 切片中降低，并且在 BE(2)-C 细胞中 RA 诱导的分化。结论：SIRT 在 NB 中具有重要的致癌特性，超出了其在衰老和基因组稳定性方面的既定功能。 SIRT6 可能代表开发未来治疗侵袭性 NB 的新疗法。
Background/Aim: Sirtuins (SIRTs) play crucial roles in various signaling pathways that modulate differentiation and proliferation. We sought to elucidate the role of SIRTs in differentiation and proliferation of human neuroblastoma (NB). Materials and Methods: NB cells were treated with nicotinamide (NAM), a non-specific SIRT inhibitor, SIRT-targeted short hairpin RNAs, and retinoic acid to assess cell growth and differentiation. Results: SIRTs are involved in proliferation and differentiation using NAM in BE(2)-C cells. Specifically, SIRT6 knockdown in BE(2)-C cells reduced cell proliferation, induced neurite extension, corresponding with induction of p21(CIP1) expression and G1 cell-cycle arrest. These effects were rescued by forced re-overexpression of SIRT6. SIRT6 expression was reduced in differentiated human NB sections, and RA-induced differentiation in BE(2)-C cells. Conclusion: SIRTs have important oncogenic properties in NB beyond its established functions in aging and genome stability. SIRT6 may represent a novel target for developing future therapeutics for the treatment of aggressive NBs.