KMT5A (known as PR-Set7/9, SETD8 and SET8), a member of the SET domain containing methyltransferase family specifically targeting H4K20 for methylation, has been implicated in multiple biological processes. In the present study, we identified that KMT5A was elevated in 50 pairs of papillary thyroid cancer tissue samples and in cell lines K1 and TPC-1 by qRT-PCR and western blotting, as well as by immunohistochemical staining. CCK-8 assay and flow cytometric analysis revealed that inhibition of KMT5A attenuated proliferation and induced apoptosis. Transwell assays revealed that cell migration and invasion were suppressed in KMT5A-knockdown cells. Moreover, the inhibition of KMT5A arrested the cell cycle in the G1/S phase of papillary thyroid cancer cells. The TCGA data revealed that elevated KMT5A expression was significantly correlated with extrathyroidal extension, lymph node metastasis and advanced pathological stage of papillary thyroid cancer. Furthermore, we observed that inhibition of KMT5A suppressed the expression of SREBP1, SCD, FASN and ACC, key molecules involved in lipid metabolism and decreased the level of malondialdehyde in papillary thyroid cancer cells. In conclusion, KMT5A may be a novel oncogenic factor, specifically a regulator for lipid metabolism in papillary thyroid carcinoma.

Epigenetic abnormalities as well as genetic abnormalities may play a vital role in the tumorigenesis of papillary thyroid cancer (PTC). The present study aimed to analyze the function and methylation status of the HOXD10 gene in PTC and aimed to identify relationships between HOXD10 methylation, HOXD10 expression, BRAF mutation and clinicopathological characteristics of PTC. A total of 152 PTC patients were enrolled in the present study. The methylation status of the HOXD10 promoter was analyzed by quantitative methylation-specific polymerase chain reaction (Q-MSP). BRAFV600E mutation status was analyzed by polymerase chain reaction (PCR) followed by DNA sequencing. HOXD10 mRNA expression level was analyzed by real-time polymerase chain reaction (RT-PCR). 5-Aza-2-deoxycytidine (5-Aza) treatment was performed in 4 PTC cell lines to observe the change in HOXD10 expression. Transwell, cell cycle and apoptosis assays were then performed in an HOXD10-overexpressing PTC cell line. Furthermore, we analyzed the associations between HOXD10 methylation, HOXD10 expression, BRAF mutation and clinicopathological characteristics in PTC. Overexpression of HOXD10 suppressed the migration of PTC cells, and promoted cell apoptosis. Q-MSP showed that methylation levels of the HOXD10 promoter were significantly higher in PTC tissues than levels in the adjacent normal thyroid tissues (P=0.02). In addition, expression of HOXD10 was decreased in the PTC cell lines and PTC tissues compared with that noted in the adjacent normal thyroid tissues (P=0.008). However, BRAFV600E mutation was detected in 42.1% of PTC patients enrolled. In addition, the BRAF mutation status was associated with the methylation and expression level of HOXD10 in PTC. We then observed that 5-Aza treatment could revert the expression of HOXD10 in PTC cell lines. Moreover, the hypermethylation of HOXD10 was associated with invasion of the primary tumor and age >45. In conclusion, the HOXD10 gene may act as a tumor suppressor in PTC. The aberrant hypermethylation and decreased expression of the HOXD10 gene were shown in PTC patients, particularly in those with BRAFV600E mutation. The epigenetic suppression of the HOXD10 gene may play a role in the tumorigenesis of PTC, and it is a prospective biomarker for the diagnosis and prognosis of PTC.

In this study, we present a case of a 52-year-old male with a chondrosarcoma of the left lamina of the thyroid cartilage. Pre-operative evaluations detected typical calcifications and delineated the extent of the tumor. The patient underwent a total laryngectomy to ensure the complete resection of the tumor. The tumor was histopathologically found to consist of chondrocytes in a hyaline cartilage matrix. The patient's post-operative course has been successful apart from the permanent tracheostomy. Herien, we discuss the methods and rationales for the diagnosis and management of and recovery from this rare tumor, and also provide a review of the literature.