环状 RNA Foxo3 促进卵巢癌细胞的进展。
Circular RNA Foxo3 enhances progression of ovarian carcinoma cells.
机构信息
Department of Gynaecology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China.
Department of Urinary Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China.
出版信息
Aging (Albany NY). 2021 Sep 23;13(18):22432-22443. doi: 10.18632/aging.203550.
BACKGROUND
Ovarian carcinoma (OC) is the deadliest gynecologic malignancy in females worldwide. Circular RNA Foxo3 (Foxo3) plays essential roles in various cancers. However, the detailed function of Foxo3 in OC remains unclear. This study aimed to investigate the role of Foxo3 in OC and the underlying molecular mechanism.
METHODS
The abundance of Foxo3 was detected in OC cell lines by qPCR. Lentivirus transduction, CCK-8, wound healing assays, transwell migration and invasion assays, luciferase reporter assay, western blotting, fluorescence hybridization (FISH), transmission electron microscopy, nanoparticle tracking analysis, and bioinformatics analysis were performed to investigate the underlying mechanism.
RESULTS
The results demonstrated that Foxo3 was significantly upregulated in OC cell lines. Overexpression and knockdown of Foxo3 promoted and inhibited the proliferation, migration, and invasion of OC cells, respectively. Foxo3 could bind to miR-422a to negatively regulate miR-422a expression. Also, proteolipid protein 2 (PLP2) was a targeting gene of miR-422a. Additionally, Foxo3 was highly expressed in exosomes derived from OC cells. Furthermore, Foxo3 could be shuttled to OC cells by exosomes and promoted OC progression.
CONCLUSIONS
Foxo3 promoted OC progression through exosome-mediated intercellular interaction to target miR-422a/PLP2 axis. Foxo3 may serve as a potential biomarker for OC.
背景
卵巢癌（OC）是全球女性中致死率最高的妇科恶性肿瘤。环状 RNA Foxo3（Foxo3）在各种癌症中发挥着重要作用。然而，Foxo3 在 OC 中的具体功能仍不清楚。本研究旨在探讨 Foxo3 在 OC 中的作用及其潜在的分子机制。
方法
通过 qPCR 检测 OC 细胞系中 Foxo3 的丰度。采用慢病毒转导、CCK-8 法、划痕愈合实验、Transwell 迁移和侵袭实验、荧光素酶报告实验、Western blot 分析、荧光原位杂交（FISH）、透射电子显微镜、纳米颗粒跟踪分析和生物信息学分析等方法来研究其潜在机制。
结果
结果表明，Foxo3 在 OC 细胞系中显著上调。Foxo3 的过表达和敲低分别促进和抑制了 OC 细胞的增殖、迁移和侵袭。Foxo3 可以与 miR-422a 结合，负调控 miR-422a 的表达。此外，蛋白脂质蛋白 2（PLP2）是 miR-422a 的靶基因。另外，Foxo3 在 OC 细胞来源的外泌体中高表达。此外，Foxo3 可以通过外泌体被转运到 OC 细胞中，并促进 OC 的进展。
结论
Foxo3 通过外泌体介导的细胞间相互作用促进 OC 进展，从而靶向 miR-422a/PLP2 轴。Foxo3 可能作为 OC 的潜在生物标志物。
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