Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
FASEB J. 2020 Apr;34(4):5208-5222. doi: 10.1096/fj.201901864RR. Epub 2020 Feb 14.
Emerging evidence highlights the role of the long noncoding RNA (lncRNA) KCNQ1OT1 in fracture healing. Osteoblast proliferation, migration, and survival are pivotal during this process. In this study, we aimed to improve our understanding of the regulatory role of lncRNA KCNQ1OT1 during osteoblast proliferation, migration, and survival. We searched the gene expression omnibus databases and LncBase Experimental V.2 to identify key microRNAs (miRNAs) targets of KCNQ1OT1. MiR-701-3p was selected as a differentially expressed miRNA and RNA immunoprecipitation assays were performed to verify its interaction with KCNQ1OT1. Fibroblast growth factor receptor 3 (FGFR3) was also identified as a target of miR-701-3p. We further identified KCNQ1OT1 as a competing endogenous RNA of miR-701-3p that could influence osteoblast proliferation, migration, and apoptosis in vitro and in vivo. Taken together, our results indicate that the KCNQ1OT1/miR-701-3p/FGFR3 axis is an important regulator of osteoblast proliferation, migration, and apoptosis, and provide a new therapeutic avenue for fracture healing.
新兴证据强调了长非编码 RNA（lncRNA）KCNQ1OT1 在骨折愈合中的作用。成骨细胞的增殖、迁移和存活在这个过程中至关重要。在这项研究中，我们旨在提高对 lncRNA KCNQ1OT1 在成骨细胞增殖、迁移和存活中的调节作用的理解。我们搜索了基因表达综合数据库和 LncBase 实验 V.2 以鉴定 KCNQ1OT1 的关键 microRNAs（miRNAs）靶标。选择 miR-701-3p 作为差异表达的 miRNA，并进行 RNA 免疫沉淀测定以验证其与 KCNQ1OT1 的相互作用。成纤维细胞生长因子受体 3（FGFR3）也被鉴定为 miR-701-3p 的靶标。我们进一步确定 KCNQ1OT1 是 miR-701-3p 的竞争性内源 RNA，可影响体外和体内成骨细胞的增殖、迁移和凋亡。总之，我们的结果表明，KCNQ1OT1/miR-701-3p/FGFR3 轴是成骨细胞增殖、迁移和凋亡的重要调节剂，并为骨折愈合提供了新的治疗途径。
