ETS1 Protein Expression May Be Altered by the Complementarity of ETS1 mRNA Sequences with miR-203a-3p and miR-204-3p...

The expressions of ETS1, miR-203a-3p, and miR-204-3p in papillary thyroid carcinoma (PTC) are poorly described, and their clinical significance is unclear. To determine the prognostic value of ETS1 (E26 transformation-specific), its levels in divergent cell compartments were paired with miR-203a-3p/-204-3p levels and linked to the presence of unfavorable clinical characteristics of PTC patients. Immunohistochemistry and Western blot were performed to evaluate ETS1 protein expression in PTC and matched nonmalignant thyroid tissue (NMT). qPCR was utilized to quantify ETS1 mRNA, miR-203a-3p, and miR-204-3p expressions. Bioinformatic analysis was applied to predict biological interactions. Although there was a significant increase in ETS1 protein expression (p < 0.05), no difference was observed in ETS1 mRNA levels between PTC and matched NMT (p > 0.05). 98.7% of PTC samples exhibited positive staining for the ETS1 protein, detected in the nucleus, the cytoplasm, or both. In contrast, the ETS1 protein had positive staining in 70.9% of NMT samples, primarily localized in the nucleus. ETS1 cytoplasmic levels correlated with the pT status of PTC patients (p = 0.020, r = -0.267), while nuclear levels correlated with the occurrence of lymph node metastasis (p = 0.020, r = -0.271). According to the bioinformatic analysis, the 3'-untranslated region of ETS1 mRNA shares a seed sequence with miR-203a-3p/-204-3p. The mutual distribution of ETS1 and miR-203a-3p levels differs between aggressive and non-aggressive PTCs. ETS1 could be used in the identification of high-risk PTC patients; however, its subcellular localization should be considered. PTC aggression could be influenced by increased cytoplasmic ETS1 protein levels, which may be affected by reduced levels of miR-203a-3p or miR-204-3p.