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HMGA2 Contributes to Distant Metastasis and Poor Prognosis by Promoting Angiogenesis in Oral Squamous Cell Carcinoma

1
Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
2
Section of Oral Oncology, Department of Oral and Maxillofacial Surgery, Fukuoka Dental College, Fukuoka 814-0193, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(10), 2473; https://doi.org/10.3390/ijms20102473
Received: 29 April 2019 / Revised: 17 May 2019 / Accepted: 18 May 2019 / Published: 19 May 2019
(This article belongs to the Special Issue Tumor Cell Invasion and Metastases)
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Abstract

The highly malignant phenotype of oral squamous cell carcinoma (OSCC), including the presence of nodal and distant metastasis, reduces patient survival. High-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor that is involved in advanced malignant phenotypes and poor prognosis in several human cancers. However, its biological role in OSCC remains to be elucidated. The purpose of this study was to determine the clinical significance and role of HMGA2 in the malignant potential of OSCC. We first investigated the expression pattern of HMGA2 and its clinical relevance in 110 OSCC specimens using immunohistochemical staining. In addition, we examined the effects HMGA2 on the regulation of vascular endothelial growth factor (VEGF)-A, VEGF-C, and fibroblast growth factor (FGF)-2, which are related to angiogenesis, in vitro. High expression of HMGA2 was significantly correlated with distant metastasis and poor prognosis. Further, HMGA2 depletion in OSCC cells reduced the expression of angiogenesis genes. In OSCC tissues with high HMGA2 expression, angiogenesis genes were increased and a high proportion of blood vessels was observed. These findings suggest that HMGA2 plays a significant role in the regulation of angiogenesis and might be a potential biomarker to predict distant metastasis and prognosis in OSCC. View Full-Text
Keywords: angiogenesis; HMGA2; metastasis; oral squamous cell carcinoma; prognosis angiogenesis; HMGA2; metastasis; oral squamous cell carcinoma; prognosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Sakata, J.; Hirosue, A.; Yoshida, R.; Kawahara, K.; Matsuoka, Y.; Yamamoto, T.; Nakamoto, M.; Hirayama, M.; Takahashi, N.; Nakamura, T.; Arita, H.; Nakashima, H.; Nagata, M.; Hiraki, A.; Shinohara, M.; Nakayama, H. HMGA2 Contributes to Distant Metastasis and Poor Prognosis by Promoting Angiogenesis in Oral Squamous Cell Carcinoma. Int. J. Mol. Sci. 2019, 20, 2473.

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