title: HMGA2 regulates epithelial-mesenchymal transition and the acquisition of tumor stem cell properties through TWIST1 in gastric cancer.
abstract: High expression of high mobility group protein A2 (HMGA2) is correlated with the invasiveness of gastric cancer and is an independent prognostic factor. The reason may be that HMGA2 promotes epithelial-mesenchymal transition (EMT) and the acquisition of tumor stem cell properties, yet the mechanism remains unclear. In this study, immunohistochemistry and western blot analysis revealed that the expression of HMGA2 and Twist-related protein 1 (TWIST1) in gastric carcinoma tissues was higher than that in the peritumoral tissues and that the expression levels of these two proteins were positively correlated. The protein expression levels of HMGA2 and TWIST1 were high in the poorly differentiated gastric cancer MKN-45 cells and were low in the moderately differentiated SGC-7901 cells. TWIST1 was inhibited after HMGA2 interference and was significantly increased after overexpression of HMGA2. Luciferase experiments showed that TWIST1 was a direct downstream target gene of HMGA2. The simultaneous interference of HMGA2 expression and the overexpression of TWIST1 in MKN-45 cells reversed the inhibitory effect of HMGA2 interference on the invasion and migration of gastric cancer cells, EMT and the expression of stemness markers. However, the simultaneous overexpression of HMGA2 and the interference of TWIST1 expression in the SGC-7901 cells reversed the promoter effect of HMGA2 overexpression on the invasiveness and migration of gastric cancer cells, EMT and the expression of stemness markers. In addition, animal experiments showed that TWIST1 overexpression reversed the inhibition of HMGA2 interference on the metastasis of MKN-45 cells. Therefore, HMGA2 regulates the EMT of gastric cancer cells and the acquisition of tumor stem cell properties through direct regulation of the downstream target gene TWIST1.
authors.affiliation: Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Lang
authors.initials: L
authors.lastname: Zha
authors.affiliation: Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Dequan
authors.initials: D
authors.lastname: Kong
authors.affiliation: Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liao
authors.affiliation: Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D051879:Twist-Related Protein 1 / Q000235:genetics*
chemical_list: D025743:HMGA2 Protein; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1