The following is a summary of “Clinical Impact of Androgen Receptor–Suppressing miR-146b Expression in Papillary Thyroid Cancer Aggressiveness,” published in the November 2023 issue of Endocrinology by Chou, et al.

Papillary thyroid carcinoma (PTC) stands as the most prevalent thyroid malignancy, with dysregulated miR-146b and androgen receptor (AR) expressions implicated in its tumorigenesis. However, the intricate mechanistic and clinical interplay between AR and miR-146b must be understood. For a study, researchers sought to elucidate miR-146b‘s role as a potential target of AR and its contribution to advanced tumor characteristics in PTC.

AR and miR-146b expression levels were evaluated in frozen and formalin-fixed paraffin-embedded tissue samples from PTC and adjacent normal thyroid specimens using quantitative real-time polymerase chain reaction. The correlation between AR and miR-146b expression was examined. Human thyroid cancer cell lines, BCPAP and TPC-1, were employed to assess the impact of AR on miR-146b signaling. Chromatin immunoprecipitation (ChIP) assays were conducted to ascertain whether AR binds to the miR-146b promoter region.

Pearson correlation analysis revealed a significant inverse correlation between miR-146b and AR expression. Overexpression of AR in BCPAP and TPC-1 cells reduced miR-146b expression. ChIP assays indicated that AR potentially binds to the androgen receptor element on the miRNA-146b gene promoter region. Furthermore, AR overexpression suppressed miR-146b-mediated tumor aggressiveness. The PTC patient subgroup characterized by low AR/high miR-146b expression exhibited advanced tumor characteristics, including higher tumor stage, lymph node metastasis, and poorer treatment response.

In conclusion, miR-146b emerged as a molecular target subjected to AR transcriptional repression. AR downregulates miR-146b expression, thereby mitigating PTC tumor aggressiveness. The findings shed light on the regulatory role of AR in PTC progression.

Source: academic.oup.com/jcem/article-abstract/108/11/2852/7176112?redirectedFrom=fulltext