Oncology Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Int J Oncol. 2023 Aug;63(2). doi: 10.3892/ijo.2023.5546. Epub 2023 Jul 14.
Despite advances in diagnosis and treatment, gastric cancer (GC) remains a refractory disease, which limits overall survival. Therefore, it is key to identify novel targets to develop more effective and precise treatment. Circular RNAs (circRNAs) serve essential roles in the process of various human cancers. Through analyzing GSE83521 dataset, the present study identified a novel circRNA derived from ribosomal protein S19 (circRPS19), which was considered a potential treatment target for GC. Results of RT‑qPCR indicated that circRPS19 was upregulated in GC compared with normal gastric epithelial cells. Loss‑of function assays revealed that silencing of circRPS19 suppressed proliferation and aerobic glycolysis but increased apoptosis of GC cells. circRPS19 upregulated ubiquitin‑specific processing protease 7 (USP7) expression by sponging microRNA (miR)‑125a‑5p. circRPS19 stabilized hexokinase 2 (HK2) protein by USP7‑mediated deubiquitination of HK2. experiments confirmed that circRPS19 promoted GC progression and aerobic glycolysis. Taken together, circRPS19 induced aerobic glycolysis of GC cells by stabilizing HK2 protein via the miR‑125a‑5p/USP7 axis and thus promoting the progression of GC. These findings suggested that circRPS19 served a critical role in the progression of GC and may be a novel therapeutic target for GC.
尽管在诊断和治疗方面取得了进展，但胃癌（GC）仍然是一种难治性疾病，这限制了总体生存率。因此，确定新的靶点以开发更有效和精确的治疗方法是关键。环状 RNA（circRNA）在各种人类癌症的发生过程中发挥着重要作用。通过分析 GSE83521 数据集，本研究鉴定了一种来自核糖体蛋白 S19 的新型环状 RNA（circRPS19），它被认为是 GC 的潜在治疗靶点。RT-qPCR 结果表明，与正常胃上皮细胞相比，GC 中 circRPS19 上调。功能丧失实验表明，circRPS19 的沉默抑制了 GC 细胞的增殖和有氧糖酵解，但增加了细胞凋亡。circRPS19 通过海绵 microRNA（miR）-125a-5p 上调泛素特异性加工蛋白酶 7（USP7）的表达。circRPS19 通过 USP7 介导的 HK2 的去泛素化稳定 HK2 蛋白。进一步的实验证实，circRPS19 通过 miR-125a-5p/USP7 轴稳定 HK2 蛋白促进 GC 细胞的有氧糖酵解和 GC 的进展。总之，circRPS19 通过稳定 HK2 蛋白促进 GC 细胞的有氧糖酵解，从而促进 GC 的进展。这些发现表明 circRPS19 在 GC 的进展中起着关键作用，可能成为 GC 的一种新的治疗靶点。
