Reduced miR-31 and let-7 maintain the balance between differentiation and quiescence in lung cancer stem-like side population cells
Reduced miR-31 and let-7 maintain the balance between differentiation and quiescence in lung cancer stem-like side population cells
复制标题
减少的miR-31和let-7维持肺癌干细胞样侧群细胞分化和静止之间的平衡
DOI：
10.1016/j.biopha.2011.09.013
复制
发表时间：
2012-03-01
影响因子：
7.5
通讯作者：
Shu Yongqian
中科院分区：
文献类型：
--
作者：
Shen Hua;Xu Xiaotao;Shu Yongqian
最近的研究表明，侧群（SP）细胞，这是一个丰富的来源，癌症干细胞（CSC），驱动和维持许多类型的人类恶性肿瘤。SP细胞具有独特的生物学特性，并被认为有助于转移、治疗抗性和肿瘤复发。在本研究中，使用miRNA阵列分析比较SP细胞和非SP细胞的miRNA表达谱。与非SP细胞相比，SP细胞中let-7和miR-31均显著下调。结果通过实时PCR证实。miR-31的工程抑制在体外引起肺癌SP细胞和非SP细胞生长的显著抑制。相反，let-7的工程抑制引起肺癌SP和非SP细胞在体外生长的显着促进。细胞周期研究进一步显示，miR-31减少可使SP细胞周期阻滞于G 0/G1期，从而抑制SP细胞增殖; let-7减少可加速SP细胞的G1/S期转换，从而促进SP细胞增殖。值得注意的是，在分化条件下，减少的miR-31阻止SP细胞分化，而减少的let-7促进SP细胞分化。这些发现表明减少的miR-31和let-7参与维持SP细胞中分化和静止之间的平衡。(c)2011年爱思唯尔马森SAS。All rights reserved.
Recent studies have indicated that side population (SP) cells, which are an enriched source of cancer stem cells (CSCs), drive and maintain many types of human malignancies. SP cells have distinguishing biological characteristics and are thought to contribute to metastasis, therapy resistance, and tumor recurrence. In the present study, the miRNA expression profiles of SP cells and non-SP cells were compared using miRNA array analysis. Both let-7 and miR-31 were significantly down-regulated in SP cells compared to non-SP cells. The results were confirmed by real-time PCR. Engineered repression of miR-31 caused marked repression of both lung cancer SP cell and non-SP cell growth in vitro. In contrast, engineered repression of let-7 caused marked promotion of both lung cancer SP and non-SP cells growth in vitro. Cell cycle studies further revealed that reduced miR-31 could inhibit SP cell proliferation by a cell cycle arrest in the G0/G1 phase, whereas reduced let-7 induced SP cell proliferation by accelerating G1/S phase transition. Notably, reduced miR-31 prevented SP cell differentiation, whereas reduced let-7 promoted SP cell differentiation under differentiation conditions. These findings indicate that reduced miR-31 and let-7 are involved in maintaining the balance between differentiation and quiescence in SP cells. (c) 2011 Elsevier Masson SAS. All rights reserved.