GRB7 在胃癌的进展中起促进作用。
GRB7 plays a promoting role in the progression of gastric cancer.
机构信息
Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
Department of General Surgery, The Affiliated Hospital of JiangXi University of Chinese Medicine, Nanchang, 330006, China.
出版信息
BMC Cancer. 2023 Dec 21;23(1):1262. doi: 10.1186/s12885-023-11694-5.
BACKGROUND
Gastric cancer is a clinically common tumor, showing an upward trend of both incidence and mortality. GRB7 has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of GRB7 in gastric cancer process.
METHODS
immunohistochemical (IHC) staining using a tissue microarray (TMA), quantitative reverse transcription PCR (qRT-PCR) and Western blotting were performed to detect the expression of genes. Furthermore, gastric cancer cell lines AGS and MGC-803 were transfected with short hairpin RNAs against GRB7. The biological function of GRB7 in gastric cancer cells were examined by CCK-8, flow cytometry, wound healing and Transwell assays. Then, in vivo tumor formation assay was conducted to explore the effects of GRB7 on tumor growth. Finally, expression levels of proteins related to cell functions were determined by Western blotting. Coimmunoprecipitation (CoIP) assay was performed to assess the protein-protein interaction.
RESULTS
GRB7 was up-regulated in gastric cancer tissues and cell lines, and its expression was inversely proportional to survival of gastric cancer patients. Moreover, GRB7 knockdown inhibited proliferative, migratory abilities, as well as promoted cell apoptosis in gastric cancer cells. Further study suggested that GRB7 silencing could suppress gastric cancer tumor growth in vivo. Furthermore, our study uncovered an important interaction between GRB7 and MyD88. Silencing MyD88 was observed to alleviate the malignant phenotypes promoted by GRB7 in gastric cancer cells.
CONCLUSIONS
Together, this study provided evidence that GRB7 may be an effective molecular targets for the treatment of gastric cancer.
背景
胃癌是一种临床常见的肿瘤，其发病率和死亡率均呈上升趋势。GRB7 已被确定为肿瘤进展的重要调节剂。本研究旨在揭示 GRB7 在胃癌发生过程中的生物学功能。
方法
采用组织微阵列（TMA）免疫组织化学（IHC）染色、定量逆转录 PCR（qRT-PCR）和 Western blot 检测基因表达。此外，AGS 和 MGC-803 胃癌细胞系用针对 GRB7 的短发夹 RNA 转染。通过 CCK-8、流式细胞术、划痕愈合和 Transwell 测定来检测 GRB7 在胃癌细胞中的生物学功能。然后，进行体内肿瘤形成实验以研究 GRB7 对肿瘤生长的影响。最后，通过 Western blot 测定与细胞功能相关的蛋白表达水平。通过共免疫沉淀（CoIP）实验评估蛋白-蛋白相互作用。
结果
GRB7 在胃癌组织和细胞系中上调，其表达与胃癌患者的生存呈负相关。此外，GRB7 敲低抑制了胃癌细胞的增殖、迁移能力，并促进了细胞凋亡。进一步的研究表明，GRB7 沉默可以抑制体内胃癌肿瘤的生长。此外，我们的研究揭示了 GRB7 与 MyD88 之间的重要相互作用。沉默 MyD88 可减轻 GRB7 在胃癌细胞中促进的恶性表型。
结论
综上所述，本研究提供了证据表明，GRB7 可能是治疗胃癌的有效分子靶标。
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