title: Downregulating HMGA2 attenuates epithelial-mesenchymal transition-induced invasion and migration in nasopharyngeal cancer cells.
abstract: BACKGROUND
  Epithelial-mesenchymal transition (EMT) is associated with invasion and metastasis of cancer cells. High-mobility group AT-hook 2 (HMGA2) has been found to play a critical role in EMT in a number of malignant tumors. However, whether HMGA2 regulates the EMT in human nasopharyngeal carcinoma (NPC) is unclear.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effect and mechanism of HMGA2 in inducing invasion and migration in NPC.
  
  
  METHODS
  In NPC tissues samples, the association of HMGA2 mRNA expression with clinicopathological characteristics were estimated by real-time quantitative RT-PCR(qRT-PCR). In vitro, following the silencing of HMGA2 in CNE-1 and CNE-2 cell lines, the viability and metastatic ability were analyzed using Cell Counting Kit-8 (CCK8), colony formation assay, and transwell assay. EMT and transforming growth factor-beta (TGFβ)/Smad3 signaling pathway-related protein expression changes were evaluated using western blot.
  
  
  RESULTS
  HMGA2 was upregulated in NPC cell lines and clinical specimens (P < 0.01), and HMGA2 expression correlated significantly with metastasis (P = 0.02) and disease-free survival of NPC (hazard ratio: 3.52; 95% confidence interval: 1.34-7.79; P = 0.01). In addition, following in vitro knockdown of HMGA2, the aggressiveness of cells was markedly inhibited, Vimentin and Snail level was downregulated and E-cadherin expression was upregulated. Moreover, the expression of key proteins TGFβRII and p-Smad3 of the TGFβ/Smad3 signaling pathway was inhibited by the downregulation of HMGA2.
  
  
  CONCLUSIONS
  HMGA2 might maintain EMT-induced invasion and migration through the TGFβ/Smad3 signaling pathway in NPC cell lines.
authors.affiliation: Department of Radiation Oncology, Lianyungang First People's Hospital, Lianyungang, Jiangsu, China; The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: You-You
authors.initials: YY
authors.lastname: Xia
authors.affiliation: Department of Radiation Oncology, The Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Radiation Oncology, The Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, The Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Guo
authors.affiliation: The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Tian
authors.affiliation: Department of Radiation Oncology, The Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xue-Song
authors.initials: XS
authors.lastname: Jiang
authors.affiliation: The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Chen
authors.affiliation: Research Center of Clinical Oncology, The Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, The Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: he_xia_2003@163.com.
authors.forename: Xia
authors.initials: X
authors.lastname: He
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D009305:Nasopharynx / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D025743:HMGA2 Protein; D034741:RNA, Small Interfering; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta
keywords: EMT; High-mobility group protein 2; NPC