Understanding the Dosage-Dependent Role of in Thyroid Tumorigenesis.

Tumors originating from thyroid follicular cells are the most common endocrine tumors, with rising incidence. Despite a generally good prognosis, up to 20% of patients experience recurrence and persistence, highlighting the need to identify the underlying molecular mechanisms. has been found to be altered in papillary thyroid cancer (PTC). Studies suggest that functions as a haploinsufficient tumor suppressor gene: partial loss promotes tumorigenesis, while complete loss prevents it. To investigate the effects of partial or total loss in PTC in vitro, we generated stable (+/-) cell lines from TPC1 using CRISPR-Cas9, though no (-/-) lines could be produced. Therefore, siRNA against was transfected into (+/-) cell lines to further decrease its expression. Transcriptomic analysis revealed changes in proliferation and cell locomotion. BrdU staining indicated a slow-down of the cell cycle, with fewer cells in S phase and more in G0-G1-phase. Additionally, transwell assays showed decreased invasion and migration after knockdown by siRNA. Moreover, overexpression led to decreased proliferation, invasion, and increased apoptosis. Our findings deepen the understanding of 's role in thyroid cancer, demonstrating that both complete elimination and overexpression of inhibit thyroid oncogenesis, highlighting as a promising target for novel therapeutic strategies.