Long non-coding RNA Mirt2 relieves lipopolysaccharide-induced injury in PC12 cells by suppressing miR-429
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Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play important roles in the pathogenesis of spinal cord injury (SCI). This study investigated the effects of lncRNA Mirt2 and miR-429 on lipopolysaccharide (LPS)-induced injuries in PC12 cells. Serum samples were collected from 36 patients with SCI and the healthy controls. The expression of lncRNA Mirt2 in serum samples was measured by qRT-PCR. The in vitro model of SCI was established by treating PC12 cells with LPS. The effects of lncRNA Mirt2 and miR-429 on the cell model were evaluated by CCK-8 assay, flow cytometry, western blot, qRT-PCR, and ELISA. Further, the activation of NF-κB and p38MAPK pathways was tested by western blot. LPS induced obvious cell injuries in PC12 cells, as cell viability was reduced, apoptosis rate was increased, caspase-3 and -9 were cleaved, and the release of TNF-α and IL-6 was induced. lncRNA Mirt2 was up-regulated in LPS-stimulated PC12 cells and serum samples derived from SCI patients. Overexpression of lncRNA Mirt2 protected PC12 cells against LPS-induced injuries. Further studies found that lncRNA Mirt2 acted as the molecular sponge of miR-429 and miR-34a-5p. lncRNA Mirt2 did not protect PC12 cells when miR-429 was overexpressed. Moreover, the inhibitory effects of lncRNA Mirt2 on NF-κB and p38MAPK pathways were abolished when miR-429 was overexpressed. lncRNA Mirt2 exerts protective effects in an in vitro model of SCI by down-regulating miR-429. This study shed light on the treatment of SCI by using the lncRNA-miRNA regulation network.
KeywordsMirt2 Spinal cord injury miR-429 Inflammation Apoptosis
Haibo Li and Yu Xu are co-first authors.
Compliance with ethical standards
Written consent was obtained from each adult volunteer before serum collection. The Ethics Committee of Affiliated Hospital of Hangzhou Normal University granted approval of this study.
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Bernhard M, Gries A, Kremer P, Bottiger BW (2005) Spinal cord injury (SCI)--prehospital management. Resuscitation 66:127–139. https://doi.org/10.1016/j.resuscitation.2005.03.005 CrossRefPubMedGoogle Scholar
- 11.Du M, Yuan L, Tan X, Huang D, Wang X, Zheng Z, Mao X, Li X, Yang L, Huang K, Zhang F, Wang Y, Luo X, Huang D, Huang K (2017) The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation. Nat Commun 8:2049. https://doi.org/10.1038/s41467-017-02229-1 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Fu S, Zhang J (2018) Knockdown of miR-429 attenuates abeta-induced neuronal damage by targeting SOX2 and BCL2 in mouse cortical neurons. 43:2240–2251. https://doi.org/10.1007/s11064-018-2643-3
- 15.Li F, Zhou MW (2019) MicroRNAs in contusion spinal cord injury: pathophysiology and clinical utility. https://doi.org/10.1007/s13760-019-01076-9
- 22.Wang J, Su B, Zhu H, Chen C, Zhao G (2016) Protective effect of geraniol inhibits inflammatory response, oxidative stress and apoptosis in traumatic injury of the spinal cord through modulation of NF-kappaB and p38 MAPK. Exp Ther Med 12:3607–3613. https://doi.org/10.3892/etm.2016.3850 CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Wang Y, Zhao X, Xie H (2019) Quality of life and its predictors in people with traumatic spinal cord injury in mainland China. Spinal Cord. https://doi.org/10.1038/s41393-019-0279-z
- 24.Xiao J, Tang J, Chen Q, Tang D, Liu M, Luo M, Wang Y, Wang J, Zhao Z, Tang C, Wang D, Mo Z (2015) miR-429 regulates alveolar macrophage inflammatory cytokine production and is involved in LPS-induced acute lung injury. Biochem J 471:281–291. https://doi.org/10.1042/bj20131510 CrossRefPubMedGoogle Scholar
- 29.Zhang Y, Cruickshanks N, Pahuski M, Yuan F, Dutta A, Schiff D, Purow B, Abounader R (2017) Noncoding RNAs in glioblastoma. In: De Vleeschouwer S (ed) Glioblastoma. Codon Publications Copyright. The Authors, Brisbane (AU). https://doi.org/10.15586/codon.glioblastoma.2017.ch6 CrossRefGoogle Scholar
- 31.Zhou HJ, Wang LQ, Wang DB, Yu JB, Zhu Y, Xu QS, Zheng XJ, Zhan RY (2018) Long noncoding RNA MALAT1 contributes to inflammatory response of microglia following spinal cord injury via the modulation of a miR-199b/IKKbeta/NF-kappaB signaling pathway. Am J Physiol Cell Physiol 315:C52–c61. https://doi.org/10.1152/ajpcell.00278.2017 CrossRefPubMedGoogle Scholar