miR-146a-3p regulates astrocyte proliferation, migration and apoptosis by inhibiting insulin-like growth factor 1 expression

doi:10.12307/2024.174

Abstract

Abstract: BACKGROUND: The alteration of miR-146a-3p level is a common event in the pathogenesis of most neurological diseases, and the specific mechanism of miR-146a-3p regulation of astrocytes has not been studied.
OBJECTIVE: To verify that miR-146a-3p regulates astrocyte proliferation, migration and apoptosis through insulin-like growth factor 1.
METHODS: 12 SD rats were divided into a sham operation group and a spinal cord injury group, with six rats in each group. RNA sequencing analysis was performed on the spinal cord tissues of all groups 2 weeks after surgery to screen out the differential genes (log2FC > 2), and to select spinal cord injury-related genes (Score > 20) in the Genecards database, and then to predict the target genes of miR-146a-3p by Targetscan. The intersection of three gene sets was obtained to screen out insulin-like growth factor 1 as one of the important target genes. qPCR, western blot assay and immunohistochemistry were performed to analyze the expression level of insulin-like growth factor 1 in spinal cord tissues. The primary astrocytes were divided into NC group, NC-mimics group and miR-146a-3p mimics group. Annexin-V/PI staining was used to detect cell apoptosis. CCK-8 assay was used to detect cell proliferation. Transwell assay was used to detect cell migration ability.
RESULTS AND CONCLUSION: The expression of miR-146a-3p in the spinal cord tissue of the spinal cord injury group was lower than that of the sham operation group (P < 0.05). The expression of insulin-like growth factor 1 in the spinal cord tissue of the spinal cord injury group was higher than that of the sham operation group (P < 0.05). Compared with the NC group and NC-mimics group, the apoptotic rate of astrocytes was increased (P < 0.01); the proliferation of astrocytes was decreased (P < 0.01) and the number of migration was decreased (P < 0.01) in the miR-146a-3p mimics group. To conclude, the expression of miR-146a-3p decreased and the expression of insulin-like growth factor 1 increased in spinal cord tissue after spinal cord injury. miR -146a-3p targeted regulation of insulin-like growth factor 1 in astrocytes, inhibited the proliferation and migration of astrocytes and promoted their apoptosis.

Key words: spinal cord injury, miR-146a-3p, insulin-like growth factor 1, astrocyte, glial scar

CLC Number:

Ye Jiapeng, Wang Jianwei, Wu Mao, Li Shaoshuo, Wang Guopeng, Wang Haotian, Tang Zhi, Shao Yang. miR-146a-3p regulates astrocyte proliferation, migration and apoptosis by inhibiting insulin-like growth factor 1 expression[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(25): 4048-4053.

Figures/Tables 5

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