Transcription Factor HOXA9 is Linked to the Calcification and Invasion of Papillary Thyroid Carcinoma

• Published in: Scientific reports Vol. 9; no. 1; p. 6773
• Main Authors: Jin, Yilan, Kim, Hyeung Kyoo, Lee, Jeonghun, Soh, Euy Young, Kim, Jang-Hee, Song, Insun, Chung, Yoon-Sok, Choi, Yong Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2019; Nature Publishing Group
• Subjects: 13/109; 13/51; 14/63; 38/77; 631/67/1459/1843; 631/80/84/2336; 82/80; Alkaline phosphatase; Apoptosis; Calcification; Calcinosis - genetics; Calcinosis - metabolism; Calcinosis - pathology; Carcinogenesis; Cbfa-1 protein; Cell adhesion & migration; Cell migration; Cell Proliferation; Chromatin; Cloning; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Homeobox; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humanities and Social Sciences; Humans; Immunoprecipitation; Invasiveness; Mineralization; Molecular modelling; multidisciplinary; Neoplasm Invasiveness; Overexpression; Papillary thyroid carcinoma; Science; Science (multidisciplinary); Thyroid; Thyroid cancer; Thyroid Cancer, Papillary - genetics; Thyroid Cancer, Papillary - metabolism; Thyroid Cancer, Papillary - pathology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; Transcription factors; Tumor Cells, Cultured; Tumorigenesis; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-43207-5

Calcification is important for the diagnosis of papillary thyroid carcinoma (PTC). Runt-related transcription factor 2 (RUNX2), a master transcription factor associated with osteogenic differentiation, is reportedly related to PTC calcification and invasiveness. However, its regulatory role in this process is somewhat uncharacterized. Here, we attempted to identify genes that regulate RUNX2 and clarify its function in PTC carcinogenesis and calcification. The expression of RUNX2-upstream genes was evaluated by real-time PCR in Nthy-Ori 3-1 normal thyroid cells and TPC1 and BHP10-3 PTC cell lines. Luciferase and chromatin immunoprecipitation assays were performed with candidate genes after cloning the
RUNX2
promoter. We found that
RUNX2
promoter activity was enhanced by homeobox family A9 (HOXA9). Over-expression of HOXA9 was found to enhance alkaline phosphatase activity, mineralization, and
in vitro
tumour cell migration and invasion, whereas downregulation had the opposite effects. These results indicate that HOXA9, a positive regulator of RUNX2, can enhance calcification, migration, and invasion in PTC. Our data improve the understanding of the molecular mechanisms of microcalcification in PTC as well as tumorigenesis.