Yang Huimin, Ji Yanxia, Ju Yingzhe, Shen Yingying, Sun Xiaoyi, Dai Kaili
Department of Oncology, Handan Central Hospital, No. 59, Congtaibei Road, Congtai District, Handan City, 056002, Hebei Province, People's Republic of China.
J Mol Histol. 2025 Sep 3;56(5):291. doi: 10.1007/s10735-025-10589-y.
Gastric cancer is a common malignancy worldwide. It has been shown that the actin cytoskeleton modulator family with sequence similarity 49 member B (FAM49B) is involved in the initiation and spread of malignancies. However, the role of FAM49B is still unknown in gastric cancer. We examined FAM49B expression in gastric cancer and its relationship between the clinical pathological features of gastric cancer patients. Lentiviruses packaged sh-FAM49B were transfected into AGS cells, and the FAM49B overexpression plasmids were transfected into HGC-27 cells to perform loss- or gain-of-function assays. Additionally, AGS cells expressing sh-FAM49B were subcutaneously injected into nude mice. In vitro and in vivo experiments were conducted to investigate the role and mechanism of FAM49B in the progresses of gastric cancer. FAM49B was upregulated in gastric cancer that indicated a poor prognosis of gastric cancer patients. FAM49B enhanced cell viability, the percent of EdU positive cells, invaded cell numbers, the relative protein expression level of PD-L1 and the IL-10 concentration, while reduced the percent of CD8 + T cells and the concentration of IFN-γ in vitro. In tumor-bearing mice, knockdown of FAM49B reduced tumor size and weight, and the protein levels of PD-L1 and IFN-γ. FAM49B promoted the expressions of the PI3K/AKT/mTOR axis in vitro and in vivo. Inhibitory role of the FAM49B knockdown in the above-mentioned progresses was reversed with the treatment of 740Y-P. Therefore, FAM49B promoted the gastric cancer cell growth, invasion and immune escape through the PI3K/AKT/mTOR axis.
胃癌是全球常见的恶性肿瘤。已有研究表明，具有序列相似性49成员B（FAM49B）的肌动蛋白细胞骨架调节剂家族参与恶性肿瘤的发生和扩散。然而，FAM49B在胃癌中的作用仍不清楚。我们检测了FAM49B在胃癌中的表达及其与胃癌患者临床病理特征的关系。将包装有sh-FAM49B的慢病毒转染到AGS细胞中，将FAM49B过表达质粒转染到HGC-27细胞中，进行功能缺失或功能获得实验。此外，将表达sh-FAM49B的AGS细胞皮下注射到裸鼠体内。进行体外和体内实验，以研究FAM49B在胃癌进展中的作用和机制。FAM49B在胃癌中上调，这表明胃癌患者预后不良。FAM49B增强了细胞活力、EdU阳性细胞百分比、侵袭细胞数量、PD-L1的相对蛋白表达水平和IL-10浓度，而在体外降低了CD8 + T细胞百分比和IFN-γ浓度。在荷瘤小鼠中，敲低FAM49B可减小肿瘤大小和重量，以及PD-L1和IFN-γ的蛋白水平。FAM49B在体外和体内均促进PI3K/AKT/mTOR轴的表达。用740Y-P处理可逆转FAM49B敲低在上述进展中的抑制作用。因此，FAM49B通过PI3K/AKT/mTOR轴促进胃癌细胞生长、侵袭和免疫逃逸。
