Pan Zhicheng, Yun Huazhong, Xiao Yun, Tong Fei, Liu Guodong, Zhang Ge, Han Jianbo
General Surgery Department, Nanjing Red Cross Hospital, Nanjing City, Jiangsu Province, 210000, China.
Iran J Public Health. 2023 Aug;52(8):1720-1729. doi: 10.18502/ijph.v52i8.13411.
In order to explore new targets for the treatment of gastric cancer (GC), we investigated the regulatory mechanism of miR-934 in the malignant phenotype of gastric cancer.
The miRNA and mRNA expressions were determined by RT-qPCR, and protein levels were quantified by western blotting assay. Malignancy of AGS cell line was evaluated by MTT, flow cytometry, wound healing and Transwell assays. The putative binding site between miR-934 and ZFP36 was validated using luciferase reporter assay. Immunohistochemistry (IHC) assay was used to visualize the ZFP36-positive cells in the xenograft sections. All experiments were conducted in General Surgery Laboratory of Nanjing Red Cross Hospital Jiangsu Province, China from June 2019 to June 2021.
GC tissues and cell lines showed notably higher levels of miR-934. Overexpression of miR-934 promoted cell viability, migration and invasion, while inhibited cell apoptosis of GC cells. ZFP36 was predicted and verified to be the target of miR-934 and low protein levels of ZFP36 were observed in GC tissues. The ZFP36 protein expressions were suppressed by miR-934 overexpression, while were facilitated by miR-934 inhibition. Furthermore, the carcinogenic functions of miR-934 were partially reversed after ZFP36 overexpression. The results of in vivo experiments further demonstrated that miR-934 promoted tumor growth and repressed the protein expression of ZFP36.
miR-934 served as a tumor promoter in GC via targeting ZFP36, and ZFP36 overexpression could efficiently relieve malignant phenotypes caused by miR-934, which prompted an exploitable molecular target for GC treatment.
为了探索胃癌（GC）治疗的新靶点，我们研究了miR-934在胃癌恶性表型中的调控机制。
通过RT-qPCR测定miRNA和mRNA表达，通过蛋白质印迹分析定量蛋白质水平。通过MTT、流式细胞术、伤口愈合和Transwell试验评估AGS细胞系的恶性程度。使用荧光素酶报告基因试验验证miR-934与ZFP36之间的假定结合位点。免疫组织化学（IHC）试验用于观察异种移植切片中ZFP36阳性细胞。所有实验于2019年6月至2021年6月在中国江苏省南京市红十字医院普通外科实验室进行。
GC组织和细胞系中miR-934水平显著升高。miR-934的过表达促进了GC细胞的活力、迁移和侵袭，同时抑制了细胞凋亡。ZFP36被预测并验证为miR-934的靶标，在GC组织中观察到ZFP36蛋白水平较低。miR-934过表达抑制了ZFP36蛋白表达，而miR-934抑制则促进了ZFP36蛋白表达。此外，ZFP36过表达后，miR-934的致癌功能部分逆转。体内实验结果进一步证明，miR-934促进肿瘤生长并抑制ZFP36蛋白表达。
miR-934通过靶向ZFP36在GC中起肿瘤促进作用，ZFP36过表达可有效缓解miR-934引起的恶性表型，这提示了一个可用于GC治疗的分子靶点。
