Abstract
Background: Circular RNAs (circRNA) have been reported to be involved in the progression of cerebral infarction. The purpose of this study was to reveal the role and potential molecular mechanism of circZfp609 (mmu_circ_0001797) in cerebral infarction. Methods: C57BL/6J mice was used to construct middle cerebral artery occlusion (MCAO) mice model, and primary mouse astrocytes were treated with oxygen-glucose deprivation/reperfusion (OGD/R) process. The circZfp609, microRNA (miR)-145a-5p and BTB and CNC homology 1 (BACH1) expression levels were detected by quantitative real-time PCR. Cell proliferation and apoptosis were assessed by cell counting kit 8 assay, EdU assay and flow cytometry. Western blot analysis was used to measure protein levels, and ELISA assay was utilized to detect the levels of inflammation factors. Lactate dehydrogenase (LDH) level was measured by LDH Assay Kit. Dual-luciferase reporter assay, RIP assay and RNA pull-down assay were used to evaluate RNA interaction. Results: CircZfp609 was upregulated in MCAO mice and OGD/R-induced astrocytes. Knockdown of circZfp609 promoted cell proliferation, while suppressed apoptosis and inflammation in OGD/R-induced astrocytes. CircZfp609 served as a sponge for miR-145a-5p, and miR-145a-5p inhibitor reversed the regulation of circZfp609 knockdown on OGD/R-induced astrocyte injury. BACH1 was a target of miR-145a-5p, and its overexpression abolished the inhibition effect of miR-145a-5p on OGD/R-induced astrocyte injury. Besides, circZfp609 downregulation also relieved the brain injury of MCAO mice through miR-145a-5p/BACH1 axis. Conclusion: Our data showed that circZfp609 might promote cerebral infarction by regulating the miR-145a-5p/BACH1 pathway.
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Qian Hu designed and performed the research; Qian Hu and Zhigang Yang analyzed the data; Ziying Zhou and Xijia Wang wrote the manuscript. All authors read and approved the final manuscript.
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Supplementary Fig. 1
The expression of circZfp609 and the target gene of miR-145a-5p. (A-B) CircZfp609 expression was detected by qRT-PCR in OGD-induced neuronal cells and OGD-induced microglia. (C) The expression of 3 genes (BACH1, EGR1 and BCL2L13) was detected by qRT-PCR in primary mouse astrocytes under miR-145a-5p mimic or miR-NC transfection. *P < 0.05.
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Zhou, Z., Wang, X., Hu, Q. et al. CircZfp609 contributes to cerebral infarction via sponging miR-145a-5p to regulate BACH1. Metab Brain Dis 38, 1971–1981 (2023). https://doi.org/10.1007/s11011-023-01208-4
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DOI: https://doi.org/10.1007/s11011-023-01208-4