Follicular thyroid carcinoma (FTC) is a common thyroid malignancy that poses diagnostic challenges because of its cytological similarity to benign follicular thyroid adenoma (FTA). The present study a Show more
Follicular thyroid carcinoma (FTC) is a common thyroid malignancy that poses diagnostic challenges because of its cytological similarity to benign follicular thyroid adenoma (FTA). The present study aimed to identify characteristic protein signatures in serum-derived extracellular vesicles (EVs) of FTC and FTA for potential diagnostic and therapeutic applications. Serum EVs from patients with FTC and FTA were purified using the phosphatidylserine affinity method. Proteomics analysis via nano liquid chromatography-tandem mass spectrometry identified 18 significantly differentially expressed proteins between the two patient groups. RAB21, a small GTPase involved in cellular trafficking, was markedly elevated in serum EVs from patients with FTC. Furthermore, cell invasion and migration assays of a human FTC cell line revealed that RAB21 knockdown reduced cell migratory ability, suggesting its role in the malignant phenotype of FTC. The present findings indicated that RAB21 in serum EVs may be a candidate biomarker able to distinguish FTC from FTA, and that RAB21 could be a potential therapeutic target for FTC. Show less
17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) converts androstenedione (A4) into testosterone (T), which regulates sex steroid production. Because various mutations of the HSD17B3 gene cause disor Show more
17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) converts androstenedione (A4) into testosterone (T), which regulates sex steroid production. Because various mutations of the HSD17B3 gene cause disorder of sex differentiation (DSD) in multiple mammalian species, it is very important to reveal the molecular characteristics of this gene in various species. Here, we revealed the open reading frame of the ovine HSD17B3 gene. Enzymatic activities of ovine HSD17B3 and HSD17B1 for converting A4 to T were detected using ovine androgen receptor-mediated transactivation in reporter assays. Although HSD17B3 also converted estrone to estradiol, this activity was much weaker than those of HSD17B1. Although ovine HSD17B3 has an amino acid sequence that is conserved compared with other mammalian species, it possesses two amino acid substitutions that are consistent with the reported variants of human HSD17B3. Substitutions of these amino acids in ovine HSD17B3 for those in human did not affect the enzymatic activities. However, enzymatic activities declined upon missense mutations of the HSD17B3 gene associated with 46,XY DSD, affecting amino acids that are conserved between these two species. The present study provides basic information and tools to investigate the molecular mechanisms behind DSD not only in ovine, but also in various mammalian species. Show less