中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (5): 1147-1153.doi: 10.4103/1673-5374.353497

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

长链非编码RNA Pvt1促进损伤周围神经许旺细胞增殖与迁移:海绵化靶向cJun的miRNA-214

  

  • 出版日期:2023-05-15 发布日期:2022-11-01
  • 基金资助:
    中国国家自然科学基金项目(81801213);徐州市科技创新促进专项基金项目(KC21177,KC21195);伊犁哈萨克族自治州科技项目(YZ2019D006)

Long noncoding RNA Pvt1 promotes the proliferation and migration of Schwann cells by sponging microRNA-214 and targeting c-Jun following peripheral nerve injury

Bin Pan1, #, Di Guo1, #, Li Jing2, Ke Li3, Xin Li1, Gen Li1, Xiao Gao1, Zhi-Wen Li4, Wei Zhao5, Hu Feng1, *, Meng-Han Cao6, *   

  1. 1Department of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China;  2Department of Orthopedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China; 3Department of Imaging, Xuzhou Central Hospital, Xuzhou, Jiangsu Province, China;  4College of Extended Education, Xuzhou Medical University, Xuzhou, Jiangsu Province, China;  5Department of Orthopedics, Kuitun Hospital, Yili Kazak Autonomous Prefecture, Xinjiang Uygur Autonomous Region, China; 6Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • Online:2023-05-15 Published:2022-11-01
  • Contact: Meng-Han Cao, MS, mhcao@xzhmu.edu.cn; Hu Feng, MS, xzfeng_hu@126.com.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, No. 81801213 (to BP); Xuzhou Special Fund for Promoting Scientific and Technological Innovation, Nos. KC21177 (to BP), KC21195 (to HF); and Science and Technology Project of Yili Kazak Autonomous Prefecture, No. YZ2019D006 (to HF). 

摘要:

最新研究发现,竞争性内源RNA广泛参与调控机体的多种生物学过程。有研究显示,长链非编码 RNA可作为竞争性内源性RNA参与周围神经的再生,但其具体的作用机制尚不明确。实验首先对小鼠挤压损伤的坐骨神经进行高通量组学和生物信息学筛选,发现调控cJun基因的竞争性内源RNA—Pvt1可在损伤后的许旺细胞中过表达,且可能通过海绵化 miRNA-214增强cJun的表达。紧接着在体外培养的许旺细胞中过表达lncRNA-Pvt1,可见许旺细胞的增殖和迁移活性明显增强,但过表达miRNA-214则可抵消lncRNA-Pvt1过表达的影响。最后体内实验中,将过表达lncRNA-Pvt1的许旺细胞注射到小鼠受损坐骨神经神经中,结果显示过表达lncRNA-Pvt1的许旺细胞可增强受损坐骨神经的再生能力,且小鼠的运动功能也明显改善。总之该结果进一步展示了长链非编码RNA在周围神经损伤修复中的作用,也以动物实验角度提出了周围神经损伤治疗的一种潜在的新靶点。

https://orcid.org/0000-0001-7984-6321 (Hu Feng); 

https://orcid.org/0000-0001-8224-660X (Meng-Han Cao); 

https://orcid.org/0000-0002-2697-8985 (Bin Pan); 

https://orcid.org/0000-0001-5140-3983 (Di Guo)

关键词: 长链非编码RNA, Pvt1, 周围神经损伤, 竞争性内源RNA, 许旺细胞, cJun, miR-214, 神经再生, 微阵列分析, 细胞迁移

Abstract: Research has shown that long-chain noncoding RNAs (lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. c-Jun plays a key role in the repair of peripheral nerve injury. However, the precise underlying mechanism of c-Jun remains unclear. In this study, we performed microarray and bioinformatics analysis of mouse crush-injured sciatic nerves and found that the lncRNA Pvt1 was overexpressed in Schwann cells after peripheral nerve injury. Mechanistic studies revealed that Pvt1 increased c-Jun expression through sponging miRNA-214. We overexpressed Pvt1 in Schwann cells cultured in vitro and found that the proliferation and migration of Schwann cells were enhanced, and overexpression of miRNA-214 counteracted the effects of Pvt1 overexpression on Schwann cell proliferation and migration. We conducted in vivo analyses and injected Schwann cells overexpressing Pvt1 into injured sciatic nerves of mice. Schwann cells overexpressing Pvt1 enhanced the regeneration of injured sciatic nerves following peripheral nerve injury and the locomotor function of mice was improved. Our findings reveal the role of lncRNAs in the repair of peripheral nerve injury and highlight lncRNA Pvt1 as a novel potential treatment target for peripheral nerve injury. 

Key words: cell migration, ceRNA, c-Jun, lncRNA, microarray, miR-214, nerve regeneration, peripheral nerve injury, Pvt1, Schwann cells