Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong Province, China.
World J Gastroenterol. 2023 May 21;29(19):2932-2949. doi: 10.3748/wjg.v29.i19.2932.
Gastrointestinal stromal tumor (GIST) is a common neoplasm with high rates of recurrence and metastasis, and its therapeutic efficacy is still not ideal. There is an unmet need to find new molecular therapeutic targets for GIST. TATA-box-binding protein-associated factor 15 (TAF15) contributes to the progress of various tumors, while the role and molecular mechanism of TAF15 in GIST progression are still unknown.
To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.
Proteomic analysis was performed to explore the differentially expressed proteins in GIST. Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines. Cell counting kit-8, colony formation, wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation, migration and invasion. A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST. Western blotting was used to detect the phosphorylation level and total level of RAF1, MEK and ERK1/2.
A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST. TAF15 was selected for the further study because of its important role in cell proliferation and migration. TAF15 was significantly over expressed in GIST tissues and cell lines. Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST. TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST and suppressed tumor growth . Moreover, the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1, MEK and ERK1/2 in GIST cells and xenograft tissues, while the total RAF1, MEK and ERK1/2 had no significant change.
TAF15 is over expressed in GIST tissues and cell lines. Overexpression of TAF15 was associated with a poor prognosis of GIST patients. TAF15 promotes cell proliferation and migration in GIST the activation of the RAF1/MEK/ERK signaling pathway. Thus, TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST.
胃肠道间质瘤（GIST）是一种常见的肿瘤，具有较高的复发和转移率，其治疗效果仍不理想。因此，有必要寻找新的 GIST 分子治疗靶点。TATA 框结合蛋白相关因子 15（TAF15）有助于各种肿瘤的进展，而 TAF15 在 GIST 进展中的作用和分子机制尚不清楚。
探讨 GIST 的新分子治疗靶点，了解 TAF15 在 GIST 进展中的生物学作用和潜在机制。
采用蛋白质组学分析方法探讨 GIST 中差异表达蛋白。Western blot 和免疫组织化学分析用于验证 TAF15 在 GIST 组织和细胞系中的表达水平。细胞计数试剂盒-8、集落形成、划痕愈合和 Transwell 实验用于检测 TAF15 对细胞增殖、迁移和侵袭能力的影响。建立 GIST 移植瘤小鼠模型，探讨 TAF15 在 GIST 进展中的作用。Western blot 用于检测 RAF1、MEK 和 ERK1/2 的磷酸化水平和总水平。
共鉴定出 1669 种差异表达蛋白，其中 762 种上调，907 种下调。由于 TAF15 在细胞增殖和迁移中具有重要作用，因此选择 TAF15 进行进一步研究。TAF15 在 GIST 组织和细胞系中明显过表达。TAF15 过表达与 GIST 肿瘤较大和风险分期较高有关。TAF15 敲低显著抑制 GIST 细胞的增殖和迁移，并抑制肿瘤生长。此外，抑制 TAF15 表达可显著降低 GIST 细胞和移植瘤组织中 RAF1、MEK 和 ERK1/2 的磷酸化水平，而 RAF1、MEK 和 ERK1/2 的总水平没有明显变化。
TAF15 在 GIST 组织和细胞系中过表达。TAF15 过表达与 GIST 患者的不良预后相关。TAF15 促进 GIST 细胞的增殖和迁移，激活 RAF1/MEK/ERK 信号通路。因此，TAF15 有望成为 GIST 的一种新的潜在分子生物标志物或治疗靶点。
