Endocrine Abstracts

Objectives: Evidence exists that estrogen receptor alpha (ERα) and beta (ERβ) may be involved in the pathogenesis of thyroid cancer. miR-341, a potent biomarker that distinguishes follicular thyroid cancer (FTC) from adenoma, has shown proliferative and metastatic effects in various cancers by regulating nuclear receptor-interacting protein 1 (NRIP1), which forms complexes with ERα. Thus, we investigated the role of miR-346 on estrogen-associated pathogenesis of FTC.

Methods: Human follicular thyroid carcinoma cell lines (FTC-133, RO82-W-1) were used. To examine the effects of estrogen and miR-346 on behavioral traits and estrogen-associated pathogenesis of FTCs, FTC-133 and RO82-W-1 were treated with 100 or 200nM of estradiol-17 β (E2) and transfected with the inhibitor targeting human miR-346. Cell migration and invasion assays were performed after the cells were transfected with either the inhibitor or the control; gene and protein levels of NRIP1, ERα, and ERβ were examined by qPCR and western blot, respectively.

Results: The expression of miR-346 was significantly higher in FTC-133 and WRO-82-1 compared to Nthy-Ori-3-1. In miR-346-downregulated FTC-133 and WRO-82-1, the trans-well assay showed that E₂, in dose-dependent manner, significantly decreased the number of invaded cells in both cell lines. Downregulation of miR-346 itself also had significant protective effects on invasion in both FTC-133 and WRO-82-1; and E₂ significantly intensified these effects in both cell lines. The similar pattern was observed in cell-migration assays. Downregulation of miR-346 significantly decreased the protein expressions of NRIP1 and ERα while increasing protein expression of Erβ. These resulted in the decreased ratio of ERα to ERβ in WRO-82-1. E₂ treatment increased the protein expression of ERβ, and downregulation of miR-346 augmented E₂-induced ERβ increase.

Conclusions: The inhibition of miR-346 resulted in the increased expression of NRIP1 and ERβ and decreased migration and invasion of FTC cells, which augmented by E2. Considering the facts that NRIP1 is the direct target of miR-346 and NRIP1 is a cofactor of ERβr, their interactions may be involved in the pathogenesis of FTC.