Long non-coding RNA TPT1-AS1 inhibits ferroptosis in ovarian cancer by regulating GPX4 via CREB1 regulation

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology Pub Date : 2024-08-14 DOI:10.1111/aji.13864

Lei Cao, Yan Wang, Juanni Liu, Xiaoying Bai, Xiaohong Chi

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引用次数: 0

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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长非编码 RNA TPT1-AS1 通过 CREB1 调节 GPX4 来抑制卵巢癌的铁突变。

背景：长非编码RNA（lncRNA）在细胞过程中发挥着关键作用，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）在包括卵巢癌（OC）在内的多种癌症中促进肿瘤进展，但其对铁突变的影响以及与其他蛋白的相互作用仍未得到充分探索：在这项研究中，我们采用了一种多方面的方法来研究 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）检测法评估了 TPT1-AS1 在 OC 标本和细胞系中的表达。功能测定包括评估 TPT1-AS1 基因敲除对 OC 细胞增殖、迁移、侵袭性和细胞周期进展的影响。此外，我们还利用生物信息学方法探索并验证了 TPT1-AS1 与其他蛋白质的相互作用。最后，我们利用铁测定法、丙二醛（MDA）测定法和活性氧（ROS）检测法研究了TPT1-AS1在麦拉宁诱导的铁变态反应中的参与情况：结果：我们的研究结果表明，TPT1-AS1在OC中的过表达与不良预后有关。TPT1-AS1基因敲除抑制了细胞的增殖、迁移和侵袭性。此外，TPT1-AS1 还能抑制麦拉宁诱导的铁凋亡，体内实验证实了它对肿瘤发生的致癌影响。机制研究发现，TPT1-AS1通过CREB1（cAMP反应元件结合蛋白1）调控谷胱甘肽过氧化物酶4（GPX4）的转录，并与RNA结合蛋白（RBP）KHDRBS3（KH RNA Binding Domain Containing, Signal Transduction Associated 3）相互作用，调控CREB1：结论：TPT1-AS1通过抑制铁凋亡和上调CREB1促进OC进展，并与KHDRBS3形成调控轴。这些发现突显了癌症进展过程中涉及 lncRNAs、RBPs 和转录因子的调控网络。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Reproductive Immunology 医学-免疫学

CiteScore

6.20

自引率

5.60%

发文量

314

审稿时长

2 months

期刊介绍： The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.