The miR-506-Induced Epithelial–Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer

Shotaro Sakimura, Keishi Sugimachi, Junji Kurashige, Masami Ueda, Hidenari Hirata, Sho Nambara, Hisateru Komatsu, Tomoko Saito, Yuki Takano, Ryutaro Uchi, Etsuko Sakimura, Yoshiaki Shinden, Tomohiro Iguchi, Hidetoshi Eguchi, Yugo Oba, Sumio Hoka, Koshi Mimori

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: MicroRNAs have roles in the regulation of the epithelial–mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer. Methods: In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3′ untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines. Results: Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P < 0.05). Low miR-506 expression was significantly correlated with high SNAI2 expression (P = 0.009) and poorly differentiated type (P = 0.015). In vitro, miR-506 suppressed SNAI2 expression by binding to its 3′UTR, resulting in increased expression of E-cadherin (P < 0.05), verified by immunohistochemical analysis. Pre-miR-506 transfected cells showed significantly suppressed cell proliferation and migration (P < 0.05) compared with the control cells. Conclusions: The EMT was directly suppressed by miR-506, and its low expression was an independent prognostic factor in gastric cancer patients. The data indicated that miR-506 may act as a tumor suppressor and could be a novel therapeutic agent.

Original languageEnglish
Pages (from-to)1436-1443
Number of pages8
JournalAnnals of Surgical Oncology
Volume22
DOIs
Publication statusPublished - Dec 1 2015

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Stomach Neoplasms
Cadherins
Cell Movement
Cell Proliferation
Patient Transfer
Survival
3' Untranslated Regions
Luciferases
MicroRNAs
Ovarian Neoplasms
Reverse Transcription
Multivariate Analysis
Breast Neoplasms
Cell Line
Polymerase Chain Reaction
Messenger RNA
Neoplasms
Proteins
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

The miR-506-Induced Epithelial–Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer. / Sakimura, Shotaro; Sugimachi, Keishi; Kurashige, Junji; Ueda, Masami; Hirata, Hidenari; Nambara, Sho; Komatsu, Hisateru; Saito, Tomoko; Takano, Yuki; Uchi, Ryutaro; Sakimura, Etsuko; Shinden, Yoshiaki; Iguchi, Tomohiro; Eguchi, Hidetoshi; Oba, Yugo; Hoka, Sumio; Mimori, Koshi.

In: Annals of Surgical Oncology, Vol. 22, 01.12.2015, p. 1436-1443.

Research output: Contribution to journalArticle

Sakimura, S, Sugimachi, K, Kurashige, J, Ueda, M, Hirata, H, Nambara, S, Komatsu, H, Saito, T, Takano, Y, Uchi, R, Sakimura, E, Shinden, Y, Iguchi, T, Eguchi, H, Oba, Y, Hoka, S & Mimori, K 2015, 'The miR-506-Induced Epithelial–Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer', Annals of Surgical Oncology, vol. 22, pp. 1436-1443. https://doi.org/10.1245/s10434-015-4418-2
Sakimura, Shotaro ; Sugimachi, Keishi ; Kurashige, Junji ; Ueda, Masami ; Hirata, Hidenari ; Nambara, Sho ; Komatsu, Hisateru ; Saito, Tomoko ; Takano, Yuki ; Uchi, Ryutaro ; Sakimura, Etsuko ; Shinden, Yoshiaki ; Iguchi, Tomohiro ; Eguchi, Hidetoshi ; Oba, Yugo ; Hoka, Sumio ; Mimori, Koshi. / The miR-506-Induced Epithelial–Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer. In: Annals of Surgical Oncology. 2015 ; Vol. 22. pp. 1436-1443.
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abstract = "Background: MicroRNAs have roles in the regulation of the epithelial–mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer. Methods: In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3′ untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines. Results: Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P < 0.05). Low miR-506 expression was significantly correlated with high SNAI2 expression (P = 0.009) and poorly differentiated type (P = 0.015). In vitro, miR-506 suppressed SNAI2 expression by binding to its 3′UTR, resulting in increased expression of E-cadherin (P < 0.05), verified by immunohistochemical analysis. Pre-miR-506 transfected cells showed significantly suppressed cell proliferation and migration (P < 0.05) compared with the control cells. Conclusions: The EMT was directly suppressed by miR-506, and its low expression was an independent prognostic factor in gastric cancer patients. The data indicated that miR-506 may act as a tumor suppressor and could be a novel therapeutic agent.",
author = "Shotaro Sakimura and Keishi Sugimachi and Junji Kurashige and Masami Ueda and Hidenari Hirata and Sho Nambara and Hisateru Komatsu and Tomoko Saito and Yuki Takano and Ryutaro Uchi and Etsuko Sakimura and Yoshiaki Shinden and Tomohiro Iguchi and Hidetoshi Eguchi and Yugo Oba and Sumio Hoka and Koshi Mimori",
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T1 - The miR-506-Induced Epithelial–Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer

AU - Sakimura, Shotaro

AU - Sugimachi, Keishi

AU - Kurashige, Junji

AU - Ueda, Masami

AU - Hirata, Hidenari

AU - Nambara, Sho

AU - Komatsu, Hisateru

AU - Saito, Tomoko

AU - Takano, Yuki

AU - Uchi, Ryutaro

AU - Sakimura, Etsuko

AU - Shinden, Yoshiaki

AU - Iguchi, Tomohiro

AU - Eguchi, Hidetoshi

AU - Oba, Yugo

AU - Hoka, Sumio

AU - Mimori, Koshi

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background: MicroRNAs have roles in the regulation of the epithelial–mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer. Methods: In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3′ untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines. Results: Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P < 0.05). Low miR-506 expression was significantly correlated with high SNAI2 expression (P = 0.009) and poorly differentiated type (P = 0.015). In vitro, miR-506 suppressed SNAI2 expression by binding to its 3′UTR, resulting in increased expression of E-cadherin (P < 0.05), verified by immunohistochemical analysis. Pre-miR-506 transfected cells showed significantly suppressed cell proliferation and migration (P < 0.05) compared with the control cells. Conclusions: The EMT was directly suppressed by miR-506, and its low expression was an independent prognostic factor in gastric cancer patients. The data indicated that miR-506 may act as a tumor suppressor and could be a novel therapeutic agent.

AB - Background: MicroRNAs have roles in the regulation of the epithelial–mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer. Methods: In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3′ untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines. Results: Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P < 0.05). Low miR-506 expression was significantly correlated with high SNAI2 expression (P = 0.009) and poorly differentiated type (P = 0.015). In vitro, miR-506 suppressed SNAI2 expression by binding to its 3′UTR, resulting in increased expression of E-cadherin (P < 0.05), verified by immunohistochemical analysis. Pre-miR-506 transfected cells showed significantly suppressed cell proliferation and migration (P < 0.05) compared with the control cells. Conclusions: The EMT was directly suppressed by miR-506, and its low expression was an independent prognostic factor in gastric cancer patients. The data indicated that miR-506 may act as a tumor suppressor and could be a novel therapeutic agent.

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