Liu Fengchao, Kong Xin, Lv Lin, Gao Jian
Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Cancer Lett. 2015 Apr 10;359(2):288-98. doi: 10.1016/j.canlet.2015.01.030. Epub 2015 Jan 26.
It has been shown that acquisition of epithelial-mesenchymal transition (EMT) and induction of cancer stem cell (CSC)-like properties contribute to metastasis of cancers in many studies; however, the molecular mechanisms underlying EMT and CSC phenotypes in liver cancer cells remain to be elucidated. MiR-155 is an important microRNA associated with tumour progression. Here, we report that miR-155 regulates not only the epithelial-mesenchymal transition but also the stem-like transition in liver cancer cells. Utilizing quantitative RT-PCR, we found that the expression of miR-155 is positively related to the levels of CD90, CD133 and Oct4 in enriched spheres. Up-regulated miR-155 significantly increases the population of stem-like CSCs among liver cancer cells and the ability to form tumour spheres. Additionally, miR-155 overexpression in cells significantly increases cell motility and invasion, as well as the epithelial-mesenchymal transition process. Conversely, suppression of miR-155 in cells had an opposite effect, which was partially rescued by the down-regulation of TP53INP1. Collectively, miR-155 promotes liver cancer cell EMT and CSCs, in part, via silencing TP53INP1. In addition, we found that TGF-β1 indirectly regulates TP53INP1 expression via miR-155 in liver cancer cells. Taken together, our findings suggest that miR-155 regulates TP53INP1 expression, to induce the epithelial-mesenchymal transition and acquisition of a stem cell phenotype.
许多研究表明，上皮-间质转化（EMT）的获得和癌干细胞（CSC）样特性的诱导促成了癌症转移；然而，肝癌细胞中EMT和CSC表型的分子机制仍有待阐明。MiR-155是一种与肿瘤进展相关的重要微小RNA。在此，我们报告miR-155不仅调节肝癌细胞的上皮-间质转化，还调节其干细胞样转化。利用定量RT-PCR，我们发现miR-155的表达与富集球中CD90、CD133和Oct4的水平呈正相关。上调的miR-155显著增加肝癌细胞中干细胞样CSC的比例以及形成肿瘤球的能力。此外，细胞中miR-155的过表达显著增加细胞的运动性和侵袭能力，以及上皮-间质转化过程。相反，抑制细胞中的miR-155则产生相反的效果，TP53INP1的下调可部分挽救这种效果。总体而言，miR-155部分通过沉默TP53INP1促进肝癌细胞的EMT和CSC形成。此外，我们发现TGF-β1在肝癌细胞中通过miR-155间接调节TP53INP1的表达。综上所述，我们的研究结果表明，miR-155调节TP53INP1的表达，以诱导上皮-间质转化和获得干细胞表型。
