Effect of GATAD1 regulating the SRRM2 gene on recurrence of thyroid tumor and its molecular mechanism

Gland Surg. 2022 Dec;11(12):1897-1907. doi: 10.21037/gs-22-666.

Abstract

Background: Thyroid blood vessels and nerves are rich, and their anatomical and physiological structures are complex. Surgery often fails to eradicate the tumor, which has a serious negative impact on the surgical outcomes and patient prognosis. Therefore, it is important to accurately predict the recurrence rate of thyroid cancer.

Methods: Based on bioinformatics analysis, the highly expressed transcription factors and differential genes in thyroid carcinoma (THCA) were obtained. Kaplan-Meier survival analysis was used to analyze the clinical effects of GATAD1 as well as SRRM2 on the recurrence of THCA patients. The effect of GATAD1 on SRRM2 expression was explored using cell experiments. Other experiments were conducted to reveal the interaction between SRRM2 and GATAD1 and their functions in THCA progression, such as cell proliferation and cell cycle.

Results: GATAD1 was overexpressed in recurrent THCA tissue compared with that in adjacent normal tissue. GATAD1 and SRRM2 were identified as the key risk factors for THCA recurrence as well as survival. Knockdown of GATAD1 and SRRM2 can inhibit THCA cell proliferation and arrest THCA cells in the G1 phase. Inhibiting GATAD1 decreased SRRM2 expression in THCA cells, whereas overexpressing GATAD1 had the opposite result. SRRM2 knockdown eliminated GATAD1-induced proliferation of THCA cells in vitro, indicating that GATAD1-induced THCA cell proliferation was dependent on increased SRRM2 expression.

Conclusions: We identified GATAD1 as an underlying diagnostic biomarker in THCA recurrence patients. The GATAD1-SRRM2 axis mediates human THCA recurrence progression and is an underlying target for THCA treatment.

Keywords: GATAD1; SRRM2; diagnostic biomarker; potential therapeutic target; thyroid carcinoma (THCA).