title: TGF-β1 acts through miR-155 to down-regulate TP53INP1 in promoting epithelial-mesenchymal transition and cancer stem cell phenotypes.
abstract: 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.
authors: Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors: Fengchao
authors: F
authors: Liu
authors: Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors: Xin
authors: X
authors: Kong
authors: Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors: Lin
authors: L
authors: Lv
authors: Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. Electronic address: g6j6@sohu.com.
authors: Jian
authors: J
authors: Gao
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms; D035683:MicroRNAs / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D006360:Heat-Shock Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C508960:TGFB1 protein, human; C429767:TP53INP1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Cancer stem cell; Epithelial–mesenchymal transition; MiR-155; TP53INP1; Tumour sphere