Endocrine Abstracts

Gender bias in the incidence of thyroid cancer is well known, however, the underlying mechanism is largely unknown. The current study determines variations in the molecular characteristics of thyroid cancers between men and women. Normal and cancerous thyroid tissues were collected from a total of 125 men and women who underwent surgical removal of the thyroid gland. Elevated levels of testosterone in serum and thyroid cancer tissues were observed in women while it decreased in men compared to respective control groups; whereas, ligand binding activity was increased in men and decreased in women. Androgen receptor (AR) mRNA expression increased in a majority of men while it decreased in a majority of women except women with follicular thyroid carcinoma (FTC). In thyroid cancers of women, Pearson’s correlation analysis showed a positive correlation of AR mRNA with AR protein, CBP and Sp1, whereas AR mRNA showed a negative correlation with p53. In case of men, AR mRNA showed a positive correlation with AR and cyclin D1 protein in papillary thyroid carcinoma (PTC); and CBP and Sp1 in follicular thyroid adenoma (FTA), whereas AR mRNA showed a positive correlation with p53. Our study identified for the first time that AR is posttranscriptionally regulated by miR-124a. Further, our in vitro studies with a PTC cell line (NPA-87-1) showed miR-124a as the potent inhibitor of AR that inhibited NPA cell proliferation even in the presence of testosterone. Thus, the current study suggests that: i) the varying pattern of testosterone level and AR status in thyroid tissues of men and women may predispose to the gender-specific incidence of thyroid tumors ii) miR-124a plays a significant role in determining the AR gene expression pattern and thus, androgen mediated thyroid tumor growth.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.