Abstract
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.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was supported by the Science and Technology Project of Nantong City (Grant Number: JC2020013) and Postgraduate Research & Practice Innovation Program of Jiangsu Province (Grant Number: KYCX21_3107), Medical Research Project of Jiangsu Commission of Health (Grant Number: ZDB2020004), and Nantong Health Commission Research Project (Grant Number: MA2021016).
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by HXH and GHX. The first draft of the manuscript was written by HXH and GHX, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Hong, H., Xu, G., Chen, J. et al. LncRNA RMRP Contributes to the Development and Progression of Spinal Cord Injury by Regulating miR-766-5p/FAM83A Axis. Mol Neurobiol 59, 6200–6210 (2022). https://doi.org/10.1007/s12035-022-02968-3
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DOI: https://doi.org/10.1007/s12035-022-02968-3