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微小 RNA-155 靶向肌球蛋白轻链激酶抑制人骨髓间充质干细胞的迁移。

MicroRNA‑155 targets myosin light chain kinase to inhibit the migration of human bone marrow‑derived mesenchymal stem cells.

机构信息

Department of Hematology, The First Affiliated Hospital, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.

Reproductive Medicine Center, The First Affiliated Hospital, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.

出版信息

Int J Mol Med. 2018 Sep;42(3):1585-1592. doi: 10.3892/ijmm.2018.3718. Epub 2018 Jun 5.

Abstract

Toll‑like receptors (TLRs) are expressed in human bone marrow‑derived mesenchymal stromal cells (BM‑MSCs). The activation of TLRs is important in the proliferation, differ-entiation, migration and hematopoiesis‑supporting functions of BM‑MSCs. MicroRNAs (miRNAs) are involved in various biological functions by mediating mRNA degradation or inhibiting the translation of target genes. Our previous study confirmed that TLRs regulate the migration ability of BM‑MSCs. It was also identified that multiple miRNAs were regulated by TLRs. In view of this, it was hypothesized that TLR‑regulated miRNAs may be important in regulating the migration of BM‑MSCs. The migration ability of BM‑MSCs was evaluated following transfection of the cells with the mimics or antagonists of miRNA (miR)‑27b, miR‑146a, miR‑155 and miR‑154. miR‑155 significantly inhibited cell migration. Myosin light chain kinase (MYLK) was identified as the direct target of miR‑155 in BM‑MSCs, which was further investigated using the luciferase reporter assay. However, miR‑155 did not affect the expression of upstream proteins of the RhoA pathway controlling the activity of MYLK, suggesting that miR‑155 directly suppressed the expression of MYLK without affecting the RhoA pathway. These results may facilitate the development and clinical use of BM‑MSCs in terms of their migration.

摘要

Toll 样受体 (TLRs) 在人骨髓间充质基质细胞 (BM-MSCs) 中表达。TLRs 的激活对 BM-MSCs 的增殖、分化、迁移和造血支持功能非常重要。MicroRNAs (miRNAs) 通过介导 mRNA 降解或抑制靶基因的翻译来参与各种生物学功能。我们之前的研究证实 TLR 调节 BM-MSCs 的迁移能力。还发现多种 miRNAs 受 TLR 调节。鉴于此,假设 TLR 调节的 miRNAs 可能在调节 BM-MSCs 的迁移中起重要作用。转染 miRNA(miR)-27b、miR-146a、miR-155 和 miR-154 的模拟物或拮抗剂后,评估 BM-MSCs 的迁移能力。miR-155 显著抑制细胞迁移。肌球蛋白轻链激酶 (MYLK) 被鉴定为 BM-MSCs 中 miR-155 的直接靶标,进一步通过荧光素酶报告基因检测进行了研究。然而,miR-155 并不影响控制 MYLK 活性的 RhoA 通路上游蛋白的表达,这表明 miR-155 直接抑制 MYLK 的表达,而不影响 RhoA 通路。这些结果可能有助于开发和临床应用 BM-MSCs 的迁移。

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