Heme-oxygenase-1: A key player in thyroid carcinoma development

Abstract

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. Lastly, 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.