Heme-oxygenase-1: a key player in thyroid carcinoma development.

Thyroid cancer is the most prevalent type of endocrine malignancy. Papillary thyroid carcinoma represents the majority of cases and is curable in approximately 90% of them, but it may also progress to anaplastic thyroid cancer, which has a poor prognosis. Therefore, the identification of new therapeutic targets remains essential. In clinical practice, HO-1 mRNA is used as a biomarker to predict malignancy in thyroid nodules. However, its role in thyroid tumor progression remains understudied, as well as its potential as a therapeutic target. In this work, we confirmed that HO-1 protein is increased in human papillary thyroid cancer tissues and further demonstrated that high HO-1 mRNA is associated with progression to anaplastic thyroid cancer. Through pharmacological modulation of human papillary and anaplastic thyroid cells, and by genetically overexpressing HO-1 variants in papillary thyroid cells, we demonstrated that the overexpression of enzymatically active HO-1 enhances cell proliferation, migration, and cell cycle progression. Finally, we demonstrated that MEK/ERK signaling is partially involved in HO-1 effects. We concluded that HO-1 plays a relevant protumor role in thyroid cancer, and it may be a promising coadjuvant therapeutic target for papillary and anaplastic thyroid cancer.