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长链非编码 RNA LINC01535 通过海绵吸附 miR-3619-5p 上调 BMP2 表达水平促进成骨分化。

lncRNA LINC01535 upregulates BMP2 expression levels to promote osteogenic differentiation via sponging miR‑3619‑5p.

机构信息

Department of Osteological Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, P.R. China.

出版信息

Mol Med Rep. 2020 Dec;22(6):5428-5435. doi: 10.3892/mmr.2020.11635. Epub 2020 Oct 26.

Abstract

Osteoporosis is a debilitating skeletal disease that causes bones to collapse and is accompanied by a high risk of bone fracture. It was previously demonstrated that the osteogenic differentiation of human bone marrow‑derived mesenchymal stem cells (hBMSCs) serves an important role in the process of human bone formation. Accumulating research has indicated that long non‑coding RNAs (lncRNAs) participate in hBMSC osteogenic differentiation. For example, LINC01535 was reported to serve as a carcinogenic factor in cervical cancer; however, its latent function and molecular mechanism in the osteogenesis of hBMSCs remain to be investigated. The present study showed that the expression levels of LINC01535 were upregulated upon increasing osteogenic differentiation time. In addition, the inhibition of LINC01535 inhibited hBMSC proliferation and osteogenic differentiation and promoted cell apoptosis. Using bioinformatics analysis, LINC01535 was discovered to have complementary binding sites for microRNA (miR)‑3619‑5p, and further experiments demonstrated that LINC01535 functioned as a sponge of miR‑3619‑5p. Additionally, bone morphogenetic protein 2 (BMP2) was confirmed to be a target of miR‑3619‑5p. The results revealed that LINC01535 regulated the expression levels of BMP2 via sponging miR‑3619‑5p. In conclusion, the findings of the present study suggested that LINC01535 may accelerate the osteogenic process of hBMSCs via targeting the miR‑3619‑5p/BMP2 axis, which may offer an innovative therapeutic method for osteoporosis.

摘要

骨质疏松症是一种使人衰弱的骨骼疾病,会导致骨骼坍塌,并伴有骨折的高风险。此前已经证明,人骨髓间充质干细胞(hBMSCs)的成骨分化在人类骨形成过程中起着重要作用。越来越多的研究表明,长链非编码 RNA(lncRNA)参与 hBMSC 成骨分化。例如,LINC01535 被报道在宫颈癌中作为致癌因子;然而,其在 hBMSC 成骨中的潜在功能和分子机制仍有待研究。本研究表明,随着成骨分化时间的增加,LINC01535 的表达水平上调。此外,抑制 LINC01535 抑制 hBMSC 增殖和成骨分化,并促进细胞凋亡。通过生物信息学分析,发现 LINC01535 与 microRNA(miR)-3619-5p 具有互补结合位点,进一步的实验表明 LINC01535 作为 miR-3619-5p 的海绵体发挥作用。此外,骨形态发生蛋白 2(BMP2)被证实是 miR-3619-5p 的靶基因。结果表明,LINC01535 通过海绵 miR-3619-5p 调节 BMP2 的表达水平。综上所述,本研究的结果表明,LINC01535 可能通过靶向 miR-3619-5p/BMP2 轴加速 hBMSC 的成骨过程,这为骨质疏松症提供了一种创新的治疗方法。

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