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降钙素基因相关肽通过 mmu_circRNA_003795 调节骨髓间充质干细胞中 FOSL2 的表达和细胞增殖。

Calcitonin gene‑related peptide regulates FOSL2 expression and cell proliferation of BMSCs via mmu_circRNA_003795.

机构信息

Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, P.R. China.

出版信息

Mol Med Rep. 2019 May;19(5):3732-3742. doi: 10.3892/mmr.2019.10038. Epub 2019 Mar 14.

Abstract

Circular RNAs (circRNAs) are a class of non‑coding RNAs that may have important regulatory potency in various biological processes. However, the role of circRNAs and their potential functions in bone marrow mesenchymal stem cells of mice (BMSCs) are still ambiguous. The current study aims to examine the expression of circRNAs and to investigate their effects on FOS like 2 AP‑1 transcription factor subunit (FOSL2) expression following stimulation of BMSCs with calcitonin gene‑related peptide (CGRP). RNA generated from BMSCs stimulated with or without CGRP was used in a microarray to detect expression of circRNAs. There were 58 significantly differentially expressed circRNAs following CGRP treatment, with 44 circRNAs downregulated and 14 upregulated. Bioinformatics analysis and regulatory networks were used to identify the potential interactions between circRNAs and microRNAs (miRs). mmu_circRNA_003795 was significantly increased in the CGRP‑stimulated BMSCs compared with the blank control. Silencing of mmu_circRNA_003795, significantly increased the expression of mmu_miR‑504‑3p, whereas FOSL2 expression and cell proliferation were decreased. Furthermore, silencing of mmu_mir‑504‑3p using an miR inhibitor led to increased FOSL2 expression. Additionally, silencing of mmu_circRNA_003795 using small interfering RNA induced marked alterations in the cell cycle of BMSCs. The results demonstrated that mmu_circRNA_003795 can indirectly regulate FOSL2 expression via sponging of miR‑504‑3p, resulting in alterations in BMSC proliferation.

摘要

环形 RNA(circRNAs)是一类非编码 RNA,它们在各种生物过程中可能具有重要的调节作用。然而,circRNAs 的作用及其在小鼠骨髓间充质干细胞(BMSCs)中的潜在功能仍然不清楚。本研究旨在检测 circRNAs 的表达,并研究其在 BMSCs 受到降钙素基因相关肽(CGRP)刺激后对 FOS 样 2 AP-1 转录因子亚基(FOSL2)表达的影响。使用 CGRP 刺激或未刺激的 BMSCs 产生的 RNA 在微阵列中检测 circRNAs 的表达。在 CGRP 处理后,有 58 个 circRNAs 的表达有显著差异,其中 44 个 circRNAs 下调,14 个上调。生物信息学分析和调控网络用于识别 circRNAs 和 microRNAs(miRs)之间的潜在相互作用。与空白对照组相比,CGRP 刺激的 BMSCs 中 mmu_circRNA_003795 显著增加。沉默 mmu_circRNA_003795 显著增加了 mmu_miR-504-3p 的表达,而 FOSL2 的表达和细胞增殖则降低。此外,用 miR 抑制剂沉默 mmu_mir-504-3p 导致 FOSL2 表达增加。此外,用小干扰 RNA 沉默 mmu_circRNA_003795 导致 BMSCs 细胞周期发生明显改变。结果表明,mmu_circRNA_003795 可以通过海绵吸附 miR-504-3p 间接调节 FOSL2 表达,从而改变 BMSC 增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e75/6472134/a56c6e50b7c2/MMR-19-05-3732-g00.jpg

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