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

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.

• Authors: Takeshi Toyozumi, Isamu Hoshino, Masahiko Takahashi, Akihiro Usui, Yasunori Akutsu, Naoyuki Hanari, Kentaro Murakami, Masayuki Kano, Naoki Akanuma, Hiroshi Suitoh, Yasunori Matsumoto, Nobuhumi Sekino, Aki Komatsu, Hisahiro Matsubara
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 24 Issue 11 Pg. 3446-3455 (Oct 2017) ISSN: 1534-4681 [Electronic] United States
• PMID: 27882471 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Proto-Oncogene Proteins c-fos
• fos-related antigen 1
• HMGA1a Protein

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Squamous Cell (genetics, metabolism, secondary, surgery)
• Cell Movement
• Cell Proliferation
• Esophageal Neoplasms (genetics, metabolism, pathology, surgery)
• Gene Expression Regulation, Neoplastic
• HMGA1a Protein (genetics, metabolism)
• Humans
• Lymphatic Metastasis
• Neoplasm Invasiveness
• Prognosis
• Proto-Oncogene Proteins c-fos (genetics, metabolism)
• Tumor Cells, Cultured