Gastroenterology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China.
Department of General Surgery, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China.
Pathol Res Pract. 2024 Nov;263:155596. doi: 10.1016/j.prp.2024.155596. Epub 2024 Sep 22.
Oxaliplatin (OXA) is a vital tool in the chemotherapy of gastric cancer (GC) patients. Circular RNAs (circRNAs) are a group of non-coding RNAs that have been associated with tumorigenesis. Nevertheless, the function of circRNAs in OXA resistance of GC is unknown.
Circ_0006089/miR-217/NRP1 were elucidated through qRT-PCR in GC OXA-tolerant tissues and cell lines. OXA half-inhibitory concentration (IC50) was quantified by MTT assay. RNA pull-down and luciferase reporter tests were applied to characterize the interaction between circ_0006089 and miR-217, miR-217 and NRP1 in GC cells.
The findings disclosed that circ_0006089 and NRP1 was heightened whereas miR-217 was dramatically declined in OXA-tolerant GC tissues and cell lines. OXA resistance was reduced and the proliferation, migration and invasion ability of OXA cells were diminished after silencing circ_0006089. In addition, circ_0006089 raised OXA resistance by sponging miR-217. Further studies revealed that miR-217 bound to NRP1 and weakened OXA resistance. In addition, it was found that circ_0006089 accelerated GC progression and OXA resistance by upregulating NRP1 expression via sponging miR-217.
Circ_0006089 regulated OXA resistance in GC cells through miR-217/NRP1 axis, implying it was a promising biomarker for GC therapy.
奥沙利铂（OXA）是胃癌（GC）患者化疗的重要工具。环状 RNA（circRNA）是一组与肿瘤发生相关的非编码 RNA。然而，circRNA 在 GC 对 OXA 耐药中的作用尚不清楚。
通过 qRT-PCR 检测 GC OXA 耐药组织和细胞系中 circ_0006089/miR-217/NRP1 的表达。MTT 法检测 OXA 半抑制浓度（IC50）。应用 RNA 下拉和荧光素酶报告基因实验鉴定 circ_0006089 与 miR-217、miR-217 与 NRP1 在 GC 细胞中的相互作用。
研究结果表明，circ_0006089 和 NRP1 在 OXA 耐药 GC 组织和细胞系中升高，而 miR-217 则显著降低。沉默 circ_0006089 可降低 OXA 耐药性，减少 OXA 细胞的增殖、迁移和侵袭能力。此外，circ_0006089 通过海绵吸附 miR-217 增加 OXA 耐药性。进一步研究表明，miR-217 与 NRP1 结合并减弱 OXA 耐药性。此外，还发现 circ_0006089 通过海绵吸附 miR-217 上调 NRP1 表达，促进 GC 进展和 OXA 耐药性。
circ_0006089 通过 miR-217/NRP1 轴调节 GC 细胞对 OXA 的耐药性，提示其可能成为 GC 治疗的有前途的标志物。
