MiR-145 regulates cancer stem-like properties and epithelial-to-mesenchymal transition in lung adenocarcinoma-initiating cells
MiR-145 regulates cancer stem-like properties and epithelial-to-mesenchymal transition in lung adenocarcinoma-initiating cells
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MiR-145 调节肺腺癌起始细胞的癌症干细胞样特性和上皮间质转化
DOI：
10.1007/s13277-014-2158-8
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发表时间：
2014-09-01
期刊：
影响因子：
--
通讯作者：
Yin, Rong
中科院分区：
文献类型：
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作者：
Hu, Jingwen;Qiu, Mantang;Yin, Rong
MicroRNA-145 (MiR-145) 是肿瘤发生的重要调节因子。我们之前的工作表明，miR-145 降低了肺腺癌细胞的增殖和侵袭以及肿瘤球生长能力。然而，潜在的分子机制仍然难以捉摸。在这里，我们报道了肺腺癌组织中miR-145的表达水平下调，并且与Oct4的表达水平呈负相关。 MiR-145 部分通过调节 Oct4 表达来抑制肺癌起始细胞 (LCIC) 的增殖。此外，我们发现 miR-145 对癌症干细胞特性产生抑制作用，并在体外抑制上皮间质转化（EMT），部分是通过调节 Oct4 来实现的。最后，我们证实了 miR-145 对体内癌症干细胞特性和 EMT 的抑制作用。综上所述，这些证据表明 miR-145 作为肿瘤抑制因子，通过靶向 Oct4 下调 LCIC 的癌症干细胞特性和 EMT 过程，从而抑制肿瘤生长和转移。
MicroRNA-145 (MiR-145) is an important regulator of tumorigenesis. Our previous work indicated that miR-145 reduced the proliferation and invasion as well as the tumorosphere growth capacity in lung adenocarcinoma cells. However, the underlying molecular mechanisms remain elusive. Here, we reported that the expression level of miR-145 was downregulated in lung adenocarcinoma tissues and negatively correlated with the expression level of Oct4. MiR-145 inhibited the proliferation of lung cancer-initiating cells (LCICs), partially by regulating Oct4 expression. Furthermore, we found that miR-145 exerted repressive effect on cancer stem cell properties and inhibited epithelial-mesenchymal transition (EMT) in vitro, also partially by regulating Oct4. Finally, we confirmed the repressive effect of miR-145 on cancer stem cell properties and EMT in vivo. Taken together, these evidences suggest that miR-145 serves as a tumor suppressor which downregulates LCICs' cancer stem cell properties and EMT process by targeting Oct4, leading to the inhibition of tumor growth and metastasis.