miR-34a-SIRT1轴的失调抑制乳腺癌干性。
Dysregulation of the miR-34a-SIRT1 axis inhibits breast cancer stemness.
作者信息
Ma Wei, Xiao Gary Guishan, Mao Jun, Lu Ying, Song Bo, Wang Lihui, Fan Shujun, Fan Panhong, Hou Zhenhuan, Li Jiazhi, Yu Xiaotang, Wang Bo, Wang Huan, Wang Honghai, Xu Fei, Li Yan, Liu Qiang, Li Lianhong
机构信息
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Department of Human Anatomy, Dalian Medical University, Dalian 116044, China.
出版信息
Oncotarget. 2015 Apr 30;6(12):10432-44. doi: 10.18632/oncotarget.3394.
Enforced expression of miR-34a eliminates cancer stem cells in some malignant tumors. Sirtuin-1 (SIRT1) is a direct target of miR-34a. Here we found low levels of miR-34a and high levels of SIRT1 in CD44+/CD24- breast cancer stem cells (BCSCs). MiR-34a overexpression and knockdown of SIRT1 decreased proportion of BSCSs and mammosphere formation. Expression of CSC markers, ALDH1, BMI1 and Nanog was decreased. In nude mice xenografts, stable expression of miR-34a and silencing of SIRT1 reduced tumor burden. Taken together, our results demonstrated that miR-34a inhibits proliferative potential of BCSCs in vitro and in vivo, at least partially by downregulating SIRT1. The miR-34a-SIRT1 axis may play role in self-renewal of BCSCs.
miR-34a的强制表达可消除某些恶性肿瘤中的癌症干细胞。沉默调节蛋白1（SIRT1）是miR-34a的直接靶点。我们发现，在CD44+/CD24-乳腺癌干细胞（BCSCs）中，miR-34a水平较低而SIRT1水平较高。miR-34a过表达和SIRT1敲低可降低BCSCs的比例和乳腺球形成。癌症干细胞标志物ALDH1、BMI1和Nanog的表达降低。在裸鼠异种移植模型中，miR-34a的稳定表达和SIRT1的沉默减轻了肿瘤负担。综上所述，我们的结果表明，miR-34a在体外和体内均可抑制BCSCs的增殖潜能，至少部分是通过下调SIRT1实现的。miR-34a-SIRT1轴可能在BCSCs的自我更新中发挥作用。
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