[Pubmed] Hsa_circ_0000313/miR-1224-3p/MKNK2 Axis Modulates CD4(+) T Cells by Activating p38 MAPK Signaling in Myasthenia

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Mediators Inflamm. 2026;2026(1):e2877539. doi: 10.1155/mi/2877539.

ABSTRACT

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder in which circular RNAs (circRNAs) are increasingly implicated, with growing evidence supporting their critical role in autoimmune pathogenesis. The role of hsa_circ_0000313 in MG, including its biological functions and mechanisms, remains unknown.

METHODS: Agarose gel electrophoresis, RNase R digestion, and Sanger sequencing were employed to verify the circular structure of hsa_circ_0000313, while nucleoplasmic separation experiment was used to determine its subcellular localization. Analysis of hsa_circ_0000313, miR-1224-3p, and MKNK2 expression was conducted via quantitative real-time PCR (qRT-PCR). CCK-8 assay and flow cytometry were employed to evaluate the proliferative capacity and apoptotic rate of Jurkat cells. ELISA detected inflammatory cytokine secretion. Potential interactions involving miR-1224-3p with either hsa_circ_0000313 or MKNK2 were predicted using bioinformatics tools and subsequently validated through dual-luciferase reporter assays. FISH assay was used to detect subcellular colocalization of hsa_circ_0000313 and miR-1224-3p.

RESULTS: We observed that compared to healthy controls, MG patients exhibited increased expression of hsa_circ_0000313 and MKNK2, along with decreased expression of miR-1224-3p. Knockdown of hsa_circ_0000313 and MKNK2, along with overexpression of miR-1224-3p, inhibited the proliferation and secretion of inflammatory factors in Jurkat cells and promoted their apoptosis. Additionally, miR-144-3p was identified as the target miRNA of hsa_circ_0000313, and MKNK2 was identified as the target gene of miR-1244-3p. Hsa_circ_AA0000313 was confirmed to be circular and resistant to RNase R digestion. There was significant colocalization of hsa_circ_0000313 with miR-1224-3p within the cytoplasm. Inhibition of miR-1244-3p reversed the effects of hsa_circ_0000313 knockdown and MKNK2 knockdown on Jurkat cells proliferation, apoptosis, and inflammatory cytokine secretion. In LPS-stimulated Jurkat cells, hsa_circ_0000313 knockdown suppressed the p38 MAPK pathway via the miR-1224-3p/MKNK2 axis, which reduced inflammatory cytokine secretion and cell proliferation as well as promoted apoptosis.

CONCLUSION: Hsa_circ_0000313 is involved in MG progression by regulating the miR-1224-3p/MKNK2 axis and can act on the p38MAPK pathway to participate in the progression of MG concomitant inflammatory infections, which may provide a promising therapeutic target in MG.

PMID:41860006 | DOI:10.1155/mi/2877539


Source: https://pubmed.ncbi.nlm.nih.gov/4186000 ... t6+133c1fe