Fra-1 Regulates the Expression of HMGA1, Which is Associated with a Poor Prognosis in Human Esophageal Squamous Cell Carcinoma
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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).
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.
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.
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.
KeywordsEsophageal Squamous Cell Carcinoma Esophageal Squamous Cell Carcinoma Patient TE11 Cell Esophageal Squamous Cell Carcinoma Cell Line Significant Independent Prognostic Factor
The authors received no funding support for this study.
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, and Hisahiro Matsubara have no disclosures to declare.