Ouyang Jun, Li Junqing, Li Dongwei, Jiang Jianlong, Hao Tengfei, Xia Yujian, Lu Xiaofang, Zhang Changhua, He Yulong
Department of Gastrointestinal Surgery, Dongguan Tungwah Hospital, Dongguan 523000, China.
Digestive Disease Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China.
Cancers (Basel). 2022 Oct 31;14(21):5381. doi: 10.3390/cancers14215381.
As an RNA-binding protein, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is involved in enhancing the progression of a few malignant tumors by recognizing N6-methyladenosine on targeted RNA. However, the specific effects of IGF2BP2 on gastric cancer (GC) and the underlying mechanisms remain unclear. In this study, the expression level of IGF2BP2 was evaluated by analyzing data from a public database and performing immunohistochemical staining with GC specimens. The effect of IGF2BP2 on GC cell metastasis was investigated by Transwell assays and animal studies. RNA immunoprecipitation (RIP) was performed to identify potential mRNA bound to IGF2BP2. The levels of these identified RNAs were measured by RT-PCR, while corresponding proteins were quantified via Western blot. It was revealed that IGF2BP2 expression in GC tissues was significantly upregulated, and its overexpression was significantly associated with worse survival in GC patients. The aberrant expression of IGF2BP2 was demonstrated to promote the invasion and metastasis of GC cells by both in vivo and in vitro experiments. In subsequent experiments, it was then verified that by directly interacting with HMGA1 mRNA, IGF2BP2 augmented its stability and thus increased its expression. The knocking down of IGF2BP2 could significantly decrease the migration and invasion of GC cells, which could be reversed by increasing HMGA1 expression. Additionally, both in vitro and in vivo epithelial-mesenchymal transition (EMT) of GC cells were enhanced by IGF2BP2/HMGA1 axis. In conclusion, it was proven in our study that the IGF2BP2/HMGA1/EMT axis contributed to GC metastasis, suggesting its potential as a novel predictive and therapeutic biomarker for GC.
作为一种RNA结合蛋白，胰岛素样生长因子2信使核糖核酸结合蛋白2（IGF2BP2）通过识别靶向RNA上的N6-甲基腺苷参与促进一些恶性肿瘤的进展。然而，IGF2BP2对胃癌（GC）的具体作用及其潜在机制仍不清楚。在本研究中，通过分析公共数据库的数据并对GC标本进行免疫组织化学染色来评估IGF2BP2的表达水平。通过Transwell实验和动物研究来探究IGF2BP2对GC细胞转移的影响。进行RNA免疫沉淀（RIP）以鉴定与IGF2BP2结合的潜在信使核糖核酸。通过逆转录聚合酶链反应（RT-PCR）测量这些鉴定出的核糖核酸的水平，同时通过蛋白质免疫印迹法对相应蛋白质进行定量。结果显示，GC组织中IGF2BP2的表达显著上调，其过表达与GC患者较差的生存率显著相关。体内和体外实验均证明，IGF2BP2的异常表达促进GC细胞的侵袭和转移。在随后的实验中，进一步证实IGF2BP2通过直接与高迁移率族蛋白A1（HMGA1）信使核糖核酸相互作用，增强其稳定性从而增加其表达。敲低IGF2BP2可显著降低GC细胞的迁移和侵袭，而增加HMGA1的表达可逆转这种情况。此外，IGF2BP2/HMGA1轴增强了GC细胞在体外和体内的上皮-间质转化（EMT）。总之，本研究证明IGF2BP2/HMGA1/EMT轴促成了GC转移，表明其作为GC新型预测和治疗生物标志物的潜力。
