First Affiliated Hospital Trauma Center, Hainan Medical University, Haikou, 570100, China.
Second Affiliated Hospital Gynecology Department, Hainan Medical University, Haikou, 570100, China.
Sci Rep. 2024 Aug 12;14(1):18720. doi: 10.1038/s41598-024-68318-6.
ARHGAP25, a member of the ARHGAP family, encodes a negative regulator of Rho-GTPase that is important for actin remodeling, cell polarity, and cell migration. ARHGAP25 is down-regulated in a variety of solid tumors and promotes cancer cell growth, migration, and invasion. However, nothing is understood about ARHGAP25's biological function in osteosarcoma. This work used qPCR and WB to confirm the expression of ARHGAP25 in osteosarcoma following the initial analysis of its expression in pan-cancer. For GO and KEGG analysis, we have chosen 300 genes from the TARGET osteosarcoma data that had the strongest positive correlation with ARHGAP25, and we created nomogram and calibration charts. We simultaneously overexpressed ARHGAP25 in osteosarcoma cells to examine its impact on apoptosis and proliferation. By using MSP, we determined their methylation status in osteosarcoma cells and normal bone cells. We observed that ARHGAP25 was significantly downregulated in a range of malignancies, including osteosarcoma, and was associated with poor patient outcomes. The decrease of ARHGAP25 expression in osteosarcoma is related to DNA methylation. Overexpression of ARHGAP25 induced apoptosis and inhibited the proliferation of osteosarcoma cells in vitro. In addition, ARHGAP25 is also associated with immune-related pathways in osteosarcoma. These findings suggest that ARHGAP25 is a valuable prognostic biomarker in osteosarcoma patients.
ARHGAP25 是 ARHGAP 家族的一员,编码 Rho-GTPase 的负向调节剂,对于肌动蛋白重塑、细胞极性和细胞迁移非常重要。ARHGAP25 在多种实体瘤中下调,并促进癌细胞生长、迁移和侵袭。然而,对于 ARHGAP25 在骨肉瘤中的生物学功能还知之甚少。本研究通过 qPCR 和 WB 对其在泛癌中的表达进行初步分析后,证实了 ARHGAP25 在骨肉瘤中的表达。为了进行 GO 和 KEGG 分析,我们从 TARGET 骨肉瘤数据中选择了与 ARHGAP25 具有最强正相关的 300 个基因,并构建了列线图和校准图。同时,我们在骨肉瘤细胞中过表达 ARHGAP25,以研究其对细胞凋亡和增殖的影响。通过 MSP,我们测定了骨肉瘤细胞和正常骨细胞中的甲基化状态。我们观察到 ARHGAP25 在多种恶性肿瘤中,包括骨肉瘤,表达明显下调,与患者预后不良相关。骨肉瘤中 ARHGAP25 表达的下调与 DNA 甲基化有关。ARHGAP25 的过表达可诱导骨肉瘤细胞凋亡并抑制其体外增殖。此外,ARHGAP25 还与骨肉瘤中的免疫相关通路有关。这些发现表明 ARHGAP25 是骨肉瘤患者有价值的预后生物标志物。