胃癌（GC）在全球癌症发病率中排名第五，在所有癌症类型中死亡率排名第三。环状RNA（circRNA）已被广泛证明可以调节GC中的多种恶性生物学行为。新的证据表明，源自 FNDC3B 的几种 circRNA 在癌症中发挥着关键作用。然而，circFNDC3B在GC中的作用仍然难以捉摸。我们通过生物信息学算法预测初步筛选出具有翻译潜力的circFNDC3B。随后，我们探索了 Sanger 测序、qRT-PCR、RNase R、RNA-FISH 和核质分级分析来评估 circ0003692（一种源自 FNDC3B 的 circRNA）的识别和定位。进行 qRT-PCR 和 ISH 来量化人 GC 组织和邻近正常组织中 circ0003692 的表达。通过双荧光素酶报告基因测定和 LC/MS 研究了 circ0003692 的蛋白质编码能力。通过体内和体外实验证实了circ0003692在GC中的生物学行为。此外，还进行了 Co-IP 和救援实验来阐明编码蛋白与 c-Myc 之间的相互作用。我们发现 circ0003692 在 GC 组织中显着下调。 Circ0003692有可能编码一种新蛋白FNDC3B-267aa，该蛋白在GC细胞中下调。我们验证了 FNDC3B-267aa（而不是 circ0003692）在体外和体内抑制 GC 迁移。从机制上讲，FNDC3B-267aa 直接与 c-Myc 相互作用，促进 c-Myc 的蛋白酶体降解，导致 c-Myc-Snail/Slug 轴下调。我们的研究表明，circ0003692 编码的新蛋白 FNDC3B-267aa 抑制 GC 转移通过与 c-Myc 结合并增强蛋白酶体介导的 c-Myc 降解。该研究提供了 circ0003692 或 FNDC3B-267aa 作为 GC 治疗靶点的潜在应用。© 2024。作者。

Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive.We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc.We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis.Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC.© 2024. The Author(s).