{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:15:58Z","timestamp":1790694958997,"version":"4.1.0"},"reference-count":32,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong High-level Hospital Construction Fund"},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"crossref","award":["SZSM201812055"],"award-info":[{"award-number":["SZSM201812055"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Pediatric nutrition support team develops scientific research projects","award":["xm-2019-000-0114-03"],"award-info":[{"award-number":["xm-2019-000-0114-03"]}]},{"name":"Research topic on academic and postgraduate education","award":["2020MSA126"],"award-info":[{"award-number":["2020MSA126"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Hepatic stellate cell (HSC) activation and hepatic fibrosis mediated biliary atresia (BA) development, but the underlying molecular mechanisms are poorly understood. This study aimed to investigate the roles of circRNA hsa_circ_0009096 in the regulation of HSC proliferation and hepatic fibrosis.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>A cellular hepatic fibrosis model was established by treating LX-2 cells with transforming growth factor \u03b2 (TGF-\u03b21). RNaseR and actinomycin D assays were performed to detect hsa_circ_0009096 stability. Expression of hsa_circ_0009096, miR-370-3p, and target genes was detected using reverse transcription-qPCR. Direct binding of hsa_circ_0009096 to miR-370-3p was validated using dual luciferase reporter assay. Cell cycle progression and apoptosis of LX-2 cells were assessed using flow cytometry. The alpha-smooth muscle actin (\u03b1-SMA), collagen 1A1 (COL1A1), and TGF beta receptor 2 (TGFBR2) protein levels in LX-2 cells were analyzed using immunocytochemistry and western blotting.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Hsa_circ_0009096 exhibited more resistance to RNase R and actinomycinD digestion than UTRN mRNA. Hsa_circ_0009096 expression increased significantly in LX-2 cells treated with TGF-\u03b21, accompanied by elevated \u03b1-SMA and COL1A1 expression. Hsa_circ_0009096 siRNAs effectively promoted miR-370-3p and suppressed TGFBR2 expression in LX-2 cells, mediated by direct association of hsa_circ_0009096 with miR-370-3p. Hsa_circ_0009096 siRNA interfered with the cell cycle progression, promoted apoptosis, and reduced \u03b1-SMA and COL1A1 expression in LX-2 cells treated with TGF-\u03b21. MiR-370-3p inhibitors mitigated the alterations in cell cycle progression, apoptosis, and \u03b1-SMA, COL1A1, and TGFBR2 expression in LX-2 cells caused by hsa_circ_0009096 siRNA. In conclusion, hsa_circ_0009096 promoted HSC proliferation and hepatic fibrosis during BA pathogenesis by accelerating TGFBR2 expression by sponging miR-370-3p.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.17356","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T07:43:26Z","timestamp":1715672606000},"page":"e17356","source":"Crossref","is-referenced-by-count":6,"title":["Hsa_circ_0009096\/miR-370-3p modulates hepatic stellate cell proliferation and fibrosis during biliary atresia 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