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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 11/2017

01-10-2017 | Translational Research and Biomarkers

Fra-1 Regulates the Expression of HMGA1, Which is Associated with a Poor Prognosis in Human Esophageal Squamous Cell Carcinoma

Authors: Takeshi Toyozumi, MD, PhD, Isamu Hoshino, MD, PhD, Masahiko Takahashi, MD, Akihiro Usui, MD, PhD, Yasunori Akutsu, MD, PhD, Naoyuki Hanari, MD, PhD, Kentaro Murakami, MD, PhD, Masayuki Kano, MD, PhD, Naoki Akanuma, MD, PhD, Hiroshi Suitoh, MD, Yasunori Matsumoto, MD, Nobuhumi Sekino, MD, Aki Komatsu, PhD, Hisahiro Matsubara, MD, PhD

Published in: Annals of Surgical Oncology | Issue 11/2017

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Abstract

Background

The expression of Fos-related antigen 1 (Fra-1) affects tumor progression, migration, and invasion. In this study, we identified the genes regulated by Fra-1 in esophageal squamous cell carcinoma (ESCC).

Methods

We constructed Fra-1 knockdown models via the transfection of small interfering RNA (siRNA) into ESCC cell lines (TE10, TE11). The expression levels of the genes in the knockdown models were analyzed using a microarray and a Biobase Upstream Analysis, while the expression levels of the candidate genes in the primary tumors of surgical specimens obtained from ESCC patients were determined using real-time polymerase chain reaction (PCR) and immunohistochemical staining. The clinicopathological features were then analyzed.

Results

The Biobase Upstream Analysis showed the high-mobility-group protein-1 (HMGA1) to be a significant gene regulated by Fra-1. Actual binding of Fra-1 to the promotor region of HMGA1 was revealed in subsequent chromatin immunoprecipitation PCR experiments. Patients with a positive HMGA1 expression had a poor prognosis, and a multivariate analysis demonstrated a positive HMGA1 expression to be a significant independent prognostic factor.

Conclusion

HMGA1 is regulated by Fra-1 in ESCC, and the HMGA1 expression is significantly associated with a poor prognosis in ESCC patients. Downregulation of the HMGA1 expression may become a practical treatment strategy against ESCC in the future.
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Metadata
Title
Fra-1 Regulates the Expression of HMGA1, Which is Associated with a Poor Prognosis in Human Esophageal Squamous Cell Carcinoma
Authors
Takeshi Toyozumi, MD, PhD
Isamu Hoshino, MD, PhD
Masahiko Takahashi, MD
Akihiro Usui, MD, PhD
Yasunori Akutsu, MD, PhD
Naoyuki Hanari, MD, PhD
Kentaro Murakami, MD, PhD
Masayuki Kano, MD, PhD
Naoki Akanuma, MD, PhD
Hiroshi Suitoh, MD
Yasunori Matsumoto, MD
Nobuhumi Sekino, MD
Aki Komatsu, PhD
Hisahiro Matsubara, MD, PhD
Publication date
01-10-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 11/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5666-5

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