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基于 circRNA-miRNA-mRNA 调控网络鉴定和表征 circCASP9 在胃癌中的作用。

Identification and Characterization of the Roles of circCASP9 in Gastric Cancer Based on a circRNA-miRNA-mRNA Regulatory Network.

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Gastrointestinal Surgery, Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, China.

出版信息

Oxid Med Cell Longev. 2022 Mar 14;2022:9416825. doi: 10.1155/2022/9416825. eCollection 2022.

Abstract

Accumulating evidence demonstrates that circular RNAs (circRNAs) have substantial effects on gastric cancer (GC) tumorigenesis and development. In this study, we performed a screen and identified two differentially expressed circRNAs (circCASP9 and circDLG5) from our circRNA microarray. We validated the expression of circCASP9 and circDLG5 in GC tissues and their normal counterparts by using qRT-PCR. Only circCASP9 was revealed to be downregulated in tumor tissues compared with adjacent normal tissues. Functionally, circCASP9 significantly inhibited the proliferation, migration, and invasion of GC cells both and . A competing endogenous RNA (ceRNA) network was constructed for the identification of candidate target genes of circCASP9. circCASP9, two miRNAs, and 55 mRNAs were selected for construction of the ceRNA network. We confirmed that circCASP9 can function as a sponge of miR-589-5p to regulate KANK1 expression, thereby controlling GC progression. Accordingly, we identified that the novel circRNA circCASP9 was differentially expressed between GC tissues and their normal counterparts. We also showed that circCASP9 can regulate the growth and metastasis of GC via the miR-589-5p/KANK1 axis. The circCASP9/miR-589-5p/KANK1 axis might provide crucial insights for investigating the occurrence and development of GC.

摘要

越来越多的证据表明,环状 RNA(circRNA)对胃癌(GC)的发生和发展有重要影响。在这项研究中,我们通过 circRNA 微阵列进行筛选,鉴定出两个差异表达的 circRNA(circCASP9 和 circDLG5)。我们通过 qRT-PCR 验证了 circCASP9 和 circDLG5 在 GC 组织及其相应正常组织中的表达。结果显示,与相邻正常组织相比,circCASP9 在肿瘤组织中表达下调。功能实验表明,circCASP9 显著抑制 GC 细胞的增殖、迁移和侵袭。构建竞争性内源性 RNA(ceRNA)网络以鉴定 circCASP9 的候选靶基因。选择 circCASP9、两个 miRNA 和 55 个 mRNA 构建 ceRNA 网络。我们证实 circCASP9 可以作为 miR-589-5p 的海绵来调节 KANK1 的表达,从而控制 GC 的进展。因此,我们确定了 circCASP9 在 GC 组织与其正常组织之间存在差异表达。我们还表明,circCASP9 可以通过 miR-589-5p/KANK1 轴调控 GC 的生长和转移。circCASP9/miR-589-5p/KANK1 轴可能为研究 GC 的发生和发展提供重要线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8a7/8938058/67376049baf7/OMCL2022-9416825.001.jpg

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