环状 RNA (circRNA) 在胰管腺癌 (PDAC) 葡萄糖代谢中的作用仍不清楚。通过对葡萄糖剥夺条件下培养的细胞进行 RNA 测序，我们鉴定出了 hsa_circ_0007590。进行 Sanger 测序以及 RNase R 和 Act D 处理以确认 hsa_circ_0007590 的环状 RNA 特征。 RNA原位杂交（RNA-ISH）和定量逆转录PCR（qRT-PCR）用于估计PDAC临床标本和细胞系中hsa_circ_0007590的表达。 hsa_circ_0007590在PDAC患者中表达较高，且与疾病的临床病理特征密切相关。细胞质-核分级分离和 FISH 测定表明 hsa_circ_0007590 位于细胞核中。进行功能获得和功能丧失测定以评估 PDAC 细胞的生物学行为。进行 Seahorse XF 测定以验证 Warburg 效应。 hsa_circ_0007590 促进 PDAC 细胞的增殖、迁移和侵袭，并促进 Warburg 效应。通过质谱、RNA Pulldown、RNA 免疫沉淀 (RIP)、RNA m6A 定量、m6A 斑点印迹、MeRIP 和蛋白质印迹来研究 hsa_circ_0007590 产生这些作用的详细机制。从机制上讲，hsa_circ_0007590 靶向 PTBP1 并增加 m6A 阅读器蛋白 YTHDF2 的表达，导致 PTEN mRNA 降解和 PI3K/AKT/mTOR 通路激活。总体而言，hsa_circ_0007590 靶向 PTBP1，通过减弱 m6A 修饰的 PTEN mRNA 的稳定性来重新编程葡萄糖代谢，并有望成为 PDAC 的治疗靶点。© 2024。作者获得 Springer Nature America, Inc 的独家许可。

The role of circular RNAs (circRNAs) in glucose metabolism in pancreatic duct adenocarcinoma (PDAC) remains elusive. Through RNA sequencing of cells cultured under conditions of glucose deprivation, we identified hsa_circ_0007590. Sanger sequencing and RNase R and Act D treatments were performed to confirm the circular RNA features of hsa_circ_0007590. RNA in situ hybridization (RNA-ISH) and quantitative reverse transcription PCR (qRT-PCR) were used to estimate hsa_circ_0007590 expression in PDAC clinical specimens and cell lines. hsa_circ_0007590 expression was higher in PDAC patients and closely related to the clinicopathological characteristics of the disease. Cytoplasm‒nuclear fractionation and FISH assays demonstrated that hsa_circ_0007590 was located in the nucleus. Gain-of-function and loss-of-function assays were performed to assess the biological behaviors of PDAC cells. Seahorse XF assays were performed to validate the Warburg effect. hsa_circ_0007590 facilitated the proliferation, migration, and invasion of PDAC cells and promoted the Warburg effect. Mass spectrometry, RNA pulldown, RNA immunoprecipitation (RIP), RNA m6A quantification, m6A dot blot, MeRIP, and Western blotting were conducted to investigate the detailed mechanism through which hsa_circ_0007590 produces these effects. Mechanistically, hsa_circ_0007590 targeted PTBP1 and increased the expression of the m6A reader protein YTHDF2, leading to PTEN mRNA degradation and PI3K/AKT/mTOR pathway activation. Overall, hsa_circ_0007590, which targets PTBP1, reprograms glucose metabolism by attenuating the stability of m6A-modified PTEN mRNA and holds potential promise as a therapeutic target for PDAC.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.