GSG2 promotes thyroid cancer via stabilizing AURKB and activating AKT pathway

Abstract

Thyroid cancer stands out as the most prevalent endocrine cancer, with its incidence on a global rise. While numerous studies have delved into the roles of GSG2 in the progression of various malignancies, its involvement in thyroid cancer remains relatively unexplored. Therefore, this study was initiated to assess the functional importance of GSG2 in human thyroid cancer development. Our findings revealed a notable upregulation of GSG2 in both thyroid cancer tissues and cell lines, demonstrating a significant correlation with the pathological stage and patients’ prognosis. Depletion of GSG2 in thyroid cancer cells resulted in suppressed malignant cell development and inhibited tumor outgrowth. Crucially, our investigation identified AURKB as a downstream gene of GSG2. GSG2 exhibited its regulatory role by stabilizing AURKB, countering SMURF1-mediated ubiquitination of AURKB. Furthermore, overexpressing AURKB restored the functional consequences of GSG2 depletion in thyroid cancer cells. Additionally, we proposed the involvement of the AKT pathway in GSG2-mediated regulation of thyroid cancer. Intriguingly, the reversal of cell phenotype alterations in GSG2-depleted cells following an AKT activator underscored the potential link between GSG2 and the AKT pathway. At the molecular level, GSG2 knockdown downregulated p-AKT, an effect partially restored after AKT activator treatment. In summary, our study concluded that GSG2 played a pivotal role in thyroid carcinogenesis, underscoring its potential as a therapeutic target for thyroid cancer.