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

Authors :
Toyozumi T
Hoshino I
Takahashi M
Usui A
Akutsu Y
Hanari N
Murakami K
Kano M
Akanuma N
Suitoh H
Matsumoto Y
Sekino N
Komatsu A
Matsubara H
Source :
Annals of surgical oncology [Ann Surg Oncol] 2017 Oct; Vol. 24 (11), pp. 3446-3455. Date of Electronic Publication: 2016 Nov 23.
Publication Year :
2017

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).<br />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.<br />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.<br />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.

Details

Language :
English
ISSN :
1534-4681
Volume :
24
Issue :
11
Database :
MEDLINE
Journal :
Annals of surgical oncology
Publication Type :
Academic Journal
Accession number :
27882471
Full Text :
https://doi.org/10.1245/s10434-016-5666-5