Endocrinology department, The Second Affiliated Hospital Zhejiang University School of Medicine, China; Endocrinology department, Sanmen People's Hospital, China.
Pathology department, Sanmen People's Hospital, China.
Int J Biochem Cell Biol. 2024 Sep;174:106635. doi: 10.1016/j.biocel.2024.106635. Epub 2024 Aug 3.
ArfGAP with coiled-coil, ankyrin repeat and PH domains 3 (ACAP3) level has been confirmed to be downregulated in papillary thyroid carcinoma (PTC). Histone deacetylase inhibitors (HDACIs) have therapeutic effects on PTC. Accordingly, this study probed into the potential relation of histone deacetylase 2 (HDAC2) and ACAP3 in PTC. Expressions of ACAP3 and HDAC2 in PTC were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between HDAC2 and ACAP3 was predicted by Pearson analysis. Cell functional assays (cell counting kit-8, transwell, wound healing and flow cytometry assays) and rescue assay were carried out to determine the effects of HDAC2/ACAP3 axis on biological behaviors of PTC cells. Expressions of apoptosis-, epithelial-mesenchymal transition-, Protein Kinase B (AKT)-, and P53-related proteins were measured by Western blot. ACAP3 level was downregulated in PTC tissues and cells. ACAP3 overexpression (oe-ACAP3) suppressed viability, proliferation, migration and invasion of PTC cells, facilitated apoptosis, downregulated the expressions of Protein Kinase B (Bcl-2) and N-cadherin, upregulated the expressions of Bcl-2 associated protein X (Bax) and E-cadherin, diminished the p-AKT/AKT ratio and elevated the p-p53/p53 ratio; however, ACAP3 silencing or HDAC2 overexpression (oe-HDAC2) did the opposite. HDAC2 negatively correlated with ACAP3. The tumor-suppressing effect of oe-ACAP3 in PTC was reversed by oe-HDAC2. Collectively, ACAP3 negatively regulated by HDAC2 suppresses the proliferation and metastasis while facilitating apoptosis of PTC cells.
ArfGAP 与卷曲螺旋、锚重复和 PH 结构域 3（ACAP3）的水平已被证实在甲状腺乳头状癌（PTC）中下调。组蛋白去乙酰化酶抑制剂（HDACIs）对 PTC 具有治疗作用。因此，本研究探讨了 PTC 中组蛋白去乙酰化酶 2（HDAC2）和 ACAP3 之间的潜在关系。通过实时定量聚合酶链反应（qRT-PCR）研究 PTC 中 ACAP3 和 HDAC2 的表达。通过 Pearson 分析预测 HDAC2 和 ACAP3 之间的关系。进行细胞功能测定（细胞计数试剂盒-8、Transwell、划痕愈合和流式细胞术测定）和挽救测定，以确定 HDAC2/ACAP3 轴对 PTC 细胞生物学行为的影响。通过 Western blot 测定凋亡、上皮-间充质转化、蛋白激酶 B（AKT）和 P53 相关蛋白的表达。ACAP3 在 PTC 组织和细胞中表达下调。ACAP3 过表达（oe-ACAP3）抑制 PTC 细胞的活力、增殖、迁移和侵袭，促进凋亡，下调蛋白激酶 B（Bcl-2）和 N-钙粘蛋白的表达，上调 Bcl-2 相关蛋白 X（Bax）和 E-钙粘蛋白的表达，降低 p-AKT/AKT 比值，升高 p-p53/p53 比值；然而，ACAP3 沉默或 HDAC2 过表达（oe-HDAC2）则相反。HDAC2 与 ACAP3 呈负相关。oe-ACAP3 在 PTC 中的肿瘤抑制作用被 oe-HDAC2 逆转。综上所述，ACAP3 受 HDAC2 的负调控，抑制 PTC 细胞的增殖和转移，同时促进凋亡。
