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通过控制Lin28b抑制胰腺癌
Sita Kugel1, Carlos Sebastián1, Julien Fitamant1
1The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Cell
|May 17, 2016
概括
Sirtuin 6 (SIRT6) 通过调节微RNA通路Lin28b来抑制胰腺癌. 损失SIRT6促进PDAC的进展和转移,在一小部分患者中确定治疗点.
科学领域:
- 癌症学
- 表观遗传学
- 分子生物学
背景情况:
- 在癌症中经常出现染色体重塑蛋白的失调.
- 这些蛋白质在瘤形成中的作用,特别是胰腺管腺癌 (PDAC) 的作用,尚不清楚.
研究的目的:
- 研究Sirtuin 6 (SIRT6) 在抑制胰腺管腺癌 (PDAC) 中的表观遗传作用.
- 确定SIRT6影响PDAC进展和转移的分子机制.
主要方法:
- 通过分子和表观遗传分析研究了SIRT6在PDAC中的功能.
- 研究了对SIRT6活性反应中的Lin28b和let-7微RNA通路的调节.
- 分析了林28b促进体中的基因组修饰和转录因子招募.
主要成果:
- 通过SIRT6的失活,PDAC的进展和转移会加速.
- 通过激素过化和Myc在Lin28b促进体的招募,SIRT6的损失导致Lin28b的上调.
- 这种表观遗传程序在30% - 40%的PDAC病例中被观察到,与预后不佳和Lin28b依赖有关.
结论:
- 在PDAC中SIRT6充当瘤抑制剂.
- 已识别的SIRT6- Lin28b表观遗传途径对PDAC的发展至关重要,并且代表了特定部分患者的潜在治疗标.
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