Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, 6-North Hai-er-xiang Road, Nantong, 226001, Jiangsu Province, China.
Mol Neurobiol. 2022 Oct;59(10):6200-6210. doi: 10.1007/s12035-022-02968-3. Epub 2022 Jul 28.
Spinal cord injury (SCI) is known as a central nervous system disorder. Previous studies suggested that long-non-coding RNA RMRP (LncRNA RMRP) was abnormally expressed in SCI, but the potential underlying mechanism remains to be further explored. To explore the regulatory roles of LncRNA RMRP/miR-766-5p/FAM83A axis in SCI. Spinal T9 hemisection was performed on healthy adult male Sprague Dawley (SD) rats to establish the SCI rat models. The expressions of LncRNA RMRP in spinal cord of rats in different groups were examined by RT-qPCR. Moreover, AGE1.HN and PC12 cells were treated with hypoxic condition, and expression of LncRNA RMRP was examined by RT-qPCR methods. Furthermore, hypoxic PC12 cells were transfected with LncRNA RMRP OE, and the cell viability, proliferation, and apoptosis were examined. Next, the direct targeting relationship between LncRNA RMRP and miR-766-5p, as well as miR-766-5p and FAM83A, was confirmed by dual-luciferase reporter and RNA pull-down assays. Finally, the effects of LncRNA RMRP/miR-766-5p/FAM83A axis on cell viability, proliferation, and apoptosis were examined. LncRNA RMRP was downregulated in SCI rats and over-expression of LncRNA RMRP alleviated the SCI condition. LncRNA RMRP over-expression increased the viability and proliferation, and inhibited the apoptosis of hypoxic PC12 cells in vitro. miR-766-5p was confirmed as a target of LncRNA RMRP, and FAM83A was confirmed as a target of miR-766-5p. LncRNA RMRP could regulate the proliferation and apoptosis of hypoxic PC12 cells via regulating miR-766-5p/FAM83A axis in vitro. LncRNA RMRP may contribute to the pathogenesis of SCI via regulating miR-766-5p/FAM83A axis.
脊髓损伤（SCI）被认为是一种中枢神经系统疾病。先前的研究表明，长链非编码 RNA RMRP（LncRNA RMRP）在 SCI 中异常表达，但潜在的机制仍有待进一步探讨。为了探讨 LncRNA RMRP/miR-766-5p/FAM83A 轴在 SCI 中的调控作用。对健康成年雄性 Sprague Dawley（SD）大鼠进行 T9 半切建立 SCI 大鼠模型。采用 RT-qPCR 检测不同组别大鼠脊髓中 LncRNA RMRP 的表达。此外，用缺氧条件处理 AGE1.HN 和 PC12 细胞，采用 RT-qPCR 方法检测 LncRNA RMRP 的表达。进一步用 LncRNA RMRP OE 转染缺氧 PC12 细胞，检测细胞活力、增殖和凋亡。接下来，通过双荧光素酶报告和 RNA 下拉实验证实 LncRNA RMRP 与 miR-766-5p 以及 miR-766-5p 与 FAM83A 之间的直接靶向关系。最后，检测 LncRNA RMRP/miR-766-5p/FAM83A 轴对细胞活力、增殖和凋亡的影响。SCI 大鼠中 LncRNA RMRP 下调，过表达 LncRNA RMRP 可减轻 SCI 症状。LncRNA RMRP 过表达可增加体外缺氧 PC12 细胞的活力和增殖，抑制其凋亡。miR-766-5p 被证实是 LncRNA RMRP 的靶标，FAM83A 被证实是 miR-766-5p 的靶标。LncRNA RMRP 可通过调控 miR-766-5p/FAM83A 轴调节体外缺氧 PC12 细胞的增殖和凋亡。LncRNA RMRP 可能通过调控 miR-766-5p/FAM83A 轴促进 SCI 的发病机制。
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