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Long Non-Coding RNA MALAT1 Promotes Acute Cerebral Infarction Through miRNAs-Mediated hs-CRP Regulation

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Abstract

The occurrence of cerebral infarction commonly takes atherosclerosis as the pathophysiological basis, accompanied by chronic inflammation. Hypersensitive C-reactive protein (hs-CRP) is an important inflammatory factor involved in the formation of atherosclerosis. This study aims to investigate the regulation of hs-CRP expression by long-chain non-coding RNA (LncRNA) MALAT1 in acute cerebral infarction patients. Plasma levels of LncRNA MALAT1 and hsa-miR-145-5p, hsa-miR-140-5p, hsa-miR-483-3p, and hsa-miR-338-3p in 256 Chinese Han ACI patients and 256 controls were analyzed. HUVECs were transfected with LncRNA MALAT1, MALAT1 NC, and si-MALAT1, respectively. The expression levels of hsa-miR-145-5p, hsa-miR-140-5p, hsa-miR-483-3p, and hsa-miR-338-3p were analyzed. Then, HUVECs were transfected with hsa-miR-145-5p inhibitor, hsa-miR-140-5p inhibitor, hsa-miR-483-3p inhibitor, hsa-miR-338-3p inhibitor, and hsa-miR-145-5p mimic, hsa-miR-140-5p mimic, hsa-miR-483-3p mimic, hsa-miR-338-3p mimic, and the expression level of hs-CRP was detected by Western blotting. The levels of hsa-miR-145-5p, hsa-miR-140-5p, hsa-miR-483-3p, and hsa-miR-338-3p in the plasma of ACI patients were significantly lower than those in the control group (p < 0.001), and the plasma LncRNA MALAT1 levels were significantly higher in ACI patients than in the control group (p < 0.001). The level of LncRNA MALAT1 in plasma of ACI patients and control group was negatively correlated with hsa-miR-145-5p, hsa-miR-140-5p, hsa-miR-483-3p, and hsa-miR-338-3p (r = − 0.36, − 0.79, − 0.76, − 0.75; − 0.60, − 0.68, − 0.48, − 0.56). Plasma levels of hsa-miR-145-5p, hsa-miR-140-5p, hsa-miR-483-3p, and hsa-miR-338-3p were negatively correlated with hs-CRP levels in patients with ACI and controls (r = − 0.74, − 0.81, − 0.84, − 0.56; − 0.61, − 0.69, − 0.69, − 0.50). MALAT1 transfection resulted in the decreased levels of hsa-miR-145-5p, hsa-miR-140-5p, hsa-miR-483-3p, and hsa-miR-338-3p in HUVECs while overexpression of hsa-miR-145-5p, hsa-miR-140-5p, hsa-miR-483-3p, and hsa-miR-338-3p led to a decrease in hs-CRP levels in HUVECs. LncRNA MALAT1 induced the upregulation of CRP expression through inhibiting the expression of hsa-miR-145-5p, hsa-miR-140-5p, hsa-miR-483-3p, and hsa-miR-338-3p.

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Funding

This study was supported by the Important Weak Subject Construction Project of Pudong Health and Family Planning Commission of Shanghai (No. PWZbr2017-06).

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Authors and Affiliations

  1. Department of Geriatric Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Pudong New Area, Shanghai, 200120, China

    Lili Teng

  2. Central Laboratory, Shanghai Oriental Hospital, Tongji University School of Medicine, Shanghai, 200120, China

    Ruifeng Meng

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  1. Lili Teng
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Correspondence to Lili Teng.

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The experimental scheme was approved by the Ethics Committee of Shanghai East Hospital, and all patients and healthy individuals signed informed consent forms.

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Teng, L., Meng, R. Long Non-Coding RNA MALAT1 Promotes Acute Cerebral Infarction Through miRNAs-Mediated hs-CRP Regulation. J Mol Neurosci 69, 494–504 (2019). https://doi.org/10.1007/s12031-019-01384-y

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  • DOI: https://doi.org/10.1007/s12031-019-01384-y

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