Department of Otolaryngology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
Department of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Dig Dis Sci. 2024 Mar;69(3):811-820. doi: 10.1007/s10620-023-08254-z. Epub 2024 Jan 13.
Gastric cancer is a common malignant tumor, and due to its insidious onset and limited screening methods, most patients are diagnosed with advanced disease and have a poor prognosis. The circRNA in exosomes has an essential role in cancer diagnosis and treatment. However, the part of hsa_circ_0014606 within exosomes in gastric cancer progression is unclear. Firstly, we extracted exosomes from the serum of gastric cancer patients and healthy individuals by ultracentrifugation and analyzed the expression of hsa_circ_0014606 in both exosomes; then knocked down hsa_circ_0014606 in vivo and in vitro, respectively, to observe its effect on the physiological function of gastric cancer cells; finally, we used bioinformatics to screen hsa_circ_0014606 targeting miRNAs and mRNAs, and experiments were performed to verify the interrelationship between the three. The results showed that the level of hsa_circ_0014606 in the serum exosomes of gastric cancer patients was significantly higher than that of the healthy population. The knockdown of hsa_circ_0014606 slowed the proliferation of gastric cancer cells, significantly reduced migration and invasion ability, accelerated apoptosis, and reduced tumor size in mice. In addition, the expression of hsa_circ_0014606 was negatively correlated with the expression of miR-514b-3p and positively correlated with the expression of heterogeneous nuclear ribonucleoprotein C (HNRNPC). In conclusion, hsa_circ_0014606 exerted a pro-cancer effect indirectly through miR-514b-3p targeting gene HNRNPC, and this study provides a new potential target for treating gastric cancer.
胃癌是一种常见的恶性肿瘤,由于其隐匿的发病和有限的筛查方法,大多数患者被诊断为晚期疾病,预后较差。外泌体中的 circRNA 在癌症的诊断和治疗中具有重要作用。然而,外泌体中 hsa_circ_0014606 在胃癌进展中的作用尚不清楚。首先,我们通过超速离心从胃癌患者和健康个体的血清中提取外泌体,并分析 hsa_circ_0014606 在两种外泌体中的表达;然后分别在体内和体外敲低 hsa_circ_0014606,观察其对胃癌细胞生理功能的影响;最后,我们使用生物信息学筛选 hsa_circ_0014606 的靶向 miRNA 和 mRNAs,并进行实验验证三者之间的相互关系。结果表明,胃癌患者血清外泌体中 hsa_circ_0014606 的水平明显高于健康人群。敲低 hsa_circ_0014606 可减缓胃癌细胞的增殖,显著降低迁移和侵袭能力,加速细胞凋亡,并减少小鼠肿瘤体积。此外,hsa_circ_0014606 的表达与 miR-514b-3p 的表达呈负相关,与异质核核糖核蛋白 C(HNRNPC)的表达呈正相关。综上所述,hsa_circ_0014606 通过靶向基因 HNRNPC 间接发挥促癌作用,本研究为治疗胃癌提供了新的潜在靶点。