Identification of UHRF2 as a Negative Regulator of Epithelial-Mesenchymal Transition and Its Clinical Significance in Esophageal Squamous Cell Carcinoma

Tomohiro Iguchi, Masami Ueda, Takaaki Masuda, Sho Nambara, Shinya Kidogami, Hisateru Komatsu, Kuniaki Sato, Taro Tobo, Yushi Ogawa, Qingjiang Hu, Tomoko Saito, Hidenari Hirata, Shotaro Sakimura, Ryutaro Uchi, Naoki Hayashi, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Yoshihiko Maehara, Koshi Mimori

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2 Citations (Scopus)

Abstract

Objective: The involvement of epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. Here, we aimed to identify EMT-related genes associated with TGF-β in ESCC and to clarify the role of these genes in the progression of ESCC. Methods: EMT-related genes associated with TGF-β expression were identified in patients with ESCC using microarray analysis and public datasets. The effects of ubiquitin-like with PHD and ring finger domains 2 (UHRF2) expression were analyzed in ESCC cell lines. Cell proliferation and invasion were measured using MTT and invasion assays, respectively. UHRF2 mRNA expression was also analyzed in 75 ESCC specimens to determine the clinical significance of UHRF2 in ESCC. Results: Treatment of ESCC cell lines with TGF-β increased UHRF2 expression. UHRF2 overexpression increased CDH1 (E-cadherin) expression and decreased invasive capacity. The 75 ESCC specimens were divided into the UHRF2 high-expression group (n = 61) and the UHRF2 low-expression group (n = 14). Low UHRF2 expression was significantly correlated with vascular invasion (p = 0.034) and was an independent prognostic factor for poor prognosis (p = 0.005). Conclusion: UHRF2 may be a negative regulator of EMT and a novel prognostic biomarker for ESCC.

Original languageEnglish
Pages (from-to)179-187
Number of pages9
JournalOncology (Switzerland)
Volume95
Issue number3
DOIs
Publication statusPublished - Aug 1 2018

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Iguchi, T., Ueda, M., Masuda, T., Nambara, S., Kidogami, S., Komatsu, H., Sato, K., Tobo, T., Ogawa, Y., Hu, Q., Saito, T., Hirata, H., Sakimura, S., Uchi, R., Hayashi, N., Ito, S., Eguchi, H., Sugimachi, K., Maehara, Y., & Mimori, K. (2018). Identification of UHRF2 as a Negative Regulator of Epithelial-Mesenchymal Transition and Its Clinical Significance in Esophageal Squamous Cell Carcinoma. Oncology (Switzerland), 95(3), 179-187. https://doi.org/10.1159/000488860