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Circ_0000376 downregulation inhibits the progression of non-small cell lung cancer by mediating the miR-488-3p/BRD4 axis and the PI3K/PKB signaling pathway

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dc.contributor.authorYuan, Hongmei
dc.contributor.authorWu, Hongge
dc.contributor.authorCheng, Jing
dc.contributor.authorXiong, Jie
dc.date.accessioned2023-02-03T10:37:19Z
dc.date.available2023-02-03T10:37:19Z
dc.date.issued2021
dc.description.abstractBackground. The involvement of circular RNAs (circRNAs) in the development of cancers has attracted much interest. This study aimed to determine the role of circ_0000376 in non-small cell lung cancer (NSCLC) and provide a new mechanism. Methods. The expression of circ_0000376, miR488-3p and bromodomain containing 4 (BRD4) mRNA was measured by quantitative real-time PCR (qPCR). Cell behaviors, including cell proliferation, invasion, migration, apoptosis and cell cycle progression were investigated using cell counting kit-8 (CCK-8) assay and colony formation assay, transwell assay, wound healing assay and flow cytometry assay, respectively. The putative relationship between miR-488-3p and circ_0000376 or BRD4 was verified by dual-luciferase reporter assay. The protein levels of BRD4 and phosphorylated PI3K/PKB were detected by western blot. Xenograft model was constructed to determine the role of circ_0000376 in vivo. Results. Circ_0000376 was highly expressed in NSCLC tissues and cells. Circ_0000376 downregulation inhibited NSCLC cell proliferation, invasion and migration, promoted cell apoptosis and cell cycle arrest and slowed tumor growth in vivo. Circ_0000376 competitively bound to miR-488-3p to regulate the expression of BRD4. Rescue experiments showed that miR-488-3p deficiency reversed the effects of circ_0000376 downregulation, and miR-488-3p restoration-suppressed cell proliferation, migration and invasion were recovered by BRD4 overexpression. Moreover, circ_0000376 downregulation weakened the levels of phosphorylated PI3K and PKB, thus reducing the activity of the PI3K/PKB pathway. Conclusion. Circ_0000376 downregulation blocked the development of NSCLC by targeting the miR-488- 3p/BRD4 network and suppressing the PI3K/PKB pathway, which broadens knowledge into the understanding of the role of circ_0000376 in NSCLC.es
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dc.format.extent16es
dc.identifier.citationHistology and Histopathology Vol. 36, nº12 (2021)
dc.identifier.doihttps://doi.org/10.14670/HH-18-390
dc.identifier.issn0213-3911
dc.identifier.issn1699-5848
dc.identifier.urihttp://hdl.handle.net/10201/128146
dc.languageenges
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologiaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectcirc_0000376es
dc.subjectmiR-488-3pes
dc.subjectBRD4es
dc.subjectNSCLCes
dc.subjectPI3K/PKBes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleCirc_0000376 downregulation inhibits the progression of non-small cell lung cancer by mediating the miR-488-3p/BRD4 axis and the PI3K/PKB signaling pathwayes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.36,nº12 (2021)