Thyroid cancer is the most common malignant tumor in the head and neck, with young and middle-aged women as the main victims (Chen et al., 2023). Papillary thyroid carcinoma (PTC), as the most important pathological type, accounts for 75–85 % of all thyroid carcinomas, and is the most universal endocrine system tumor (Abdullah et al., 2019, Yu et al., 2021). Treatment of PTC primarily resorts to surgery clinically, with a ten-year survival rate of more than 95 % and a five-year mortality rate of less than 2 % (Pizzato et al., 2022). Nevertheless, nodule recurrence occurs in approximately 20 % of patients. Lymph node metastasis is a contributor for PTC recurrence, during which primary PTC metastasizes to and colonizes lymph nodes, and then induces new lymphangiogenesis, so that PTC can transmit to a distant place through the lymphatic vessels (Rezzola et al., 2022). Therefore, inhibiting the metastasis of PTC may be an important strategy to improve the prognosis of PTC patients.
A recent study has found that ArfGAP with coiled-coil, ankyrin repeat and PH domains 3 (ACAP3) gene is imbalanced in PTC, which may be a vital indicator for prognosis of PTC patients (Lin et al., 2021). ACAP3 (also known as CENTB5) is a GTPase-activating protein that specifically activates the small GTPase Arf6, thereby participating in the regulation of Arf6-dependent cell adhesion, dendritic differentiation, membrane transport, and cell movement (Hongu et al., 2016, Miura and Kanaho, 2017). At present, research on ACAP3 mostly focuses on nervous system diseases, such as Parkinson’s disease and epilepsy (Suchkova et al., 2020), and mainly discusses the function of ACAP3 regulating the migration of neurons in cerebral cortex. Hence, there are no available data regarding the role of ACAP3 in PTC, and the secret of its imbalance in PTC is yet to be uncovered.
Histone deacetylase inhibitors (HDACIs) have been confirmed to possibly serve as promising anti-PTC agents (Spartalis et al., 2021). This is because histone acetylation can relax the chromatin structure and open the binding sites of transcription factors in the promoter region of genes, so that the transcription factors can bind to the corresponding sites more easily, thus promoting the transcription of genes. However, histone deacetylation tightens the chromatin structure and blocks the transcription factors from entering the corresponding sites, resulting in gene silencing (Chen and Liu, 2022). Of note, highly expressed HDAC2 has been identified in thyroid cancer (Borbone et al., 2010). We analyzed the promoter region of ACAP3 through hTFtarget database (https://guolab.wchscu.cn/hTFtarget/#! /), and found ACAP3 could bind to HDAC2. Accordingly, we inferred that HDAC2 may inhibit ACAP3 expression, and thus reduce the apoptosis of cancer cells, leading to malignant progression of PTC. Here, we investigated whether HDAC2 negatively regulates ACAP3 to repress the malignant development of PTC cells.