长链非编码 RNA (lncRNA) 在细胞过程中发挥着至关重要的作用，其失调与包括癌症在内的多种疾病有关。 lncRNA TPT1-AS1（TPT1反义RNA 1）可促进多种癌症的肿瘤进展，包括卵巢癌（OC），但其对铁死亡的影响以及与其他蛋白质的相互作用仍有待探索。在这项研究中，我们采用了多方面的方法研究 TPT1-AS1 在 OC 中的功能意义。我们使用 RT-qPCR、原位杂交 (ISH) 和荧光原位杂交 (FISH) 测定评估了 OC 标本和细胞系中的 TPT1-AS1 表达。功能测定包括评估 TPT1-AS1 敲低对 OC 细胞增殖、迁移、侵袭和细胞周期进展的影响。此外，我们利用生物信息学探索并验证了 TPT1-AS1 与其他蛋白质的相互作用。最后，我们使用铁测定、丙二醛 (MDA) 测定和活性氧 (ROS) 检测研究了 TPT1-AS1 在erastin诱导的铁死亡中的参与情况。我们的研究结果表明，OC 中 TPT1-AS1 过度表达与不良预后相关。 TPT1-AS1 敲低可抑制细胞增殖、迁移和侵袭。此外，TPT1-AS1 抑制erastin 诱导的铁死亡，体内实验证实了其对肿瘤发展的致癌影响。从机制上讲，TPT1-AS1被发现通过CREB1（cAMP反应元件结合蛋白1）调节谷胱甘肽过氧化物酶4（GPX4）转录，并与RNA结合蛋白（RBP）KHDRBS3（包含KH RNA结合域，信号转导相关3）相互作用TPT1-AS1 通过抑制铁死亡和上调 CREB1，与 KHDRBS3 形成调节轴来促进 OC 进展。这些发现强调了癌症进展中涉及 lncRNA、RBP 和转录因子的调控网络。© 2024 John Wiley

Long non-coding RNAs (lncRNAs) play crucial roles in cellular processes, with dysregulation implicated in various diseases, including cancers. The lncRNA TPT1-AS1 (TPT1 Antisense RNA 1) promotes tumor progression in several cancers, including ovarian cancer (OC), but its influence on ferroptosis and interaction with other proteins remains underexplored.In this study, we employed a multi-faceted approach to investigate the functional significance of TPT1-AS1 in OC. We assessed TPT1-AS1 expression in OC specimens and cell lines using RT-qPCR, in situ hybridization (ISH), and fluorescence in situ hybridization (FISH) assays. Functional assays included evaluating the impact of TPT1-AS1 knockdown on OC cell proliferation, migration, invasiveness, and cell cycle progression. Further, we explored and validated the interaction of TPT1-AS1 with other proteins using bioinformatics. Finally, we investigated TPT1-AS1 involvement in erastin-induced ferroptosis using Iron Assay, Malondialdehyde (MDA) assay, and reactive oxygen species (ROS) detection.Our findings revealed that TPT1-AS1 overexpression in OC correlated with an unfavorable prognosis. TPT1-AS1 knockdown suppressed cell proliferation, migration, and invasiveness. Additionally, TPT1-AS1 inhibited erastin-induced ferroptosis, and in vivo experiments confirmed its oncogenic impact on tumor development. Mechanistically, TPT1-AS1 was found to regulate Glutathione Peroxidase 4 (GPX4) transcription via CREB1 (cAMP response element-binding protein 1) and interact with RNA-binding protein (RBP) KHDRBS3 (KH RNA Binding Domain Containing, Signal Transduction Associated 3) to regulate CREB1.TPT1-AS1 promotes OC progression by inhibiting ferroptosis and upregulating CREB1, forming a regulatory axis with KHDRBS3. These findings highlight the regulatory network involving lncRNAs, RBPs, and transcription factors in cancer progression.© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.