Knockdown of KDM1A suppresses tumour migration and invasion by epigenetically regulating the TIMP1/MMP9 pathway in papillary thyroid cancer

• Published in: Journal of cellular and molecular medicine 2019-08, Vol.23 (8), p.4933-4944
• Main Authors: Zhang, WenQian, Sun, Wei, Qin, Yuan, Wu, CangHao, He, Liang, Zhang, Ting, Shao, Liang, Zhang, Hao, Zhang, Ping
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Brain cancer; Cell adhesion & migration; Cell culture; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cervical cancer; Chromatin Immunoprecipitation; Demethylation; Design of experiments; DNA methylation; Epigenesis, Genetic; Epigenetics; Female; Gelatinase B; Gene expression; Gene Expression Regulation, Neoplastic - genetics; H3K4me2; Histone Demethylases - genetics; Histone Demethylases - metabolism; Histone H3; Histones; Histones - chemistry; Histones - metabolism; Hospitals; Humans; Invasiveness; KDM1A; Kinases; Lymph nodes; lymphatic metastasis; Lymphatic Metastasis - genetics; Lymphatic system; Lysine; Male; Matrix metalloproteinase; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Medical prognosis; Metalloproteinase; Metastases; Metastasis; Mice; Mice, Nude; Middle Aged; Original; Papillary thyroid cancer; Promoter Regions, Genetic; Proteins; Therapeutic applications; Thyroid cancer; Thyroid Cancer, Papillary - enzymology; Thyroid Cancer, Papillary - genetics; Thyroid Cancer, Papillary - metabolism; Thyroid Cancer, Papillary - secondary; Thyroid Neoplasms - enzymology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; TIMP1; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Transplantation, Heterologous; Tumorigenesis; Tumors
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.14311

Epigenetic dysregulation plays an important role in cancer. Histone demethylation is a well‐known mechanism of epigenetic regulation that promotes or inhibits tumourigenesis in various malignant tumours. However, the pathogenic role of histone demethylation modifiers in papillary thyroid cancer (PTC), which has a high incidence of early lymphatic metastasis, is largely unknown. Here, we detected the expression of common histone demethylation modifiers and found that the histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) demethylase KDM1A (or lysine demethylase 1A) is frequently overexpressed in PTC tissues and cell lines. High KDM1A expression correlated positively with age