A novel lncRNA LNC_000052 leads to the dysfunction of osteoporotic BMSCs via the miR-96-5p-PIK3R1 axis.
A novel lncRNA LNC_000052 leads to the dysfunction of osteoporotic BMSCs via the miR-96-5p-PIK3R1 axis.
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DOI：
10.1038/s41419-020-03006-7
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发表时间：
2020-09-23
影响因子：
9
通讯作者：
Fu Q
中科院分区：
文献类型：
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作者：
Li M;Cong R;Yang L;Yang L;Zhang Y;Fu Q
绝经后骨质疏松症模型中的骨髓间充质干细胞（BMSC）表现出活力和多能性的丧失。鉴定骨质疏松 BMSC 中差异表达的 RNA 可以揭示生理条件下 BMSC 功能障碍的机制，这可能会改善干细胞治疗和组织再生。在本研究中，我们进行了高通量RNA测序，结果表明新型长非编码RNA（lncRNA）LNC_000052及其共表达的mRNA PIK3R1在骨质疏松BMSC中表达上调。敲低 LNC_000052 可以促进 BMSC 增殖、迁移、成骨，并通过 PI3K/Akt 信号通路抑制细胞凋亡。我们发现 LNC_000052 和 PIK3R1 共享一个 miRNA 靶标 miR-96-5p，该靶标在骨质疏松 BMSC 中下调。它们的结合位点通过双荧光素酶测定得到证实。 miR-96-5p的下调可以抑制LNC_000052敲低的效果，而miR-96-5p的上调与LNC_000052敲低一起可以提高BMSC的治疗效果。总之，LNC_000052–miR-96-5p–PIK3R1 轴导致骨质疏松 BMSC 功能障碍，可能成为干细胞治疗和组织再生的新治疗靶点。
Bone marrow-derived mesenchymal stem cells (BMSCs) in postmenopausal osteoporosis models exhibit loss of viability and multipotency. Identification of the differentially expressed RNAs in osteoporotic BMSCs could reveal the mechanisms underlying BMSC dysfunction under physiological conditions, which might improve stem cell therapy and tissue regeneration. In this study, we performed high-throughput RNA sequencing and showed that the novel long non-coding RNA (lncRNA) LNC_000052 and its co-expressed mRNA PIK3R1 were upregulated in osteoporotic BMSCs. Knockdown of LNC_000052 could promote BMSC proliferation, migration, osteogenesis, and inhibit apoptosis via the PI3K/Akt signaling pathway. We found that both LNC_000052 and PIK3R1 shared a miRNA target, miR-96-5p, which was downregulated in osteoporotic BMSCs. Their binding sites were confirmed by dual-luciferase assays. Downregulation of miR-96-5p could restrain the effects of LNC_000052 knockdown while upregulation of miR-96-5p together with LNC_000052 knockdown could improve the therapeutic effects of BMSCs. In summary, the LNC_000052–miR-96-5p–PIK3R1 axis led to dysfunction of osteoporotic BMSCs and might be a novel therapeutic target for stem cell therapy and tissue regeneration.
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影响因子：
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作者：
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通讯作者：
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DOI：
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