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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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Yuan-36-1309-1324-2021.pdf(19.38 MB)
Date
2021
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Authors
Yuan, Hongmei ; Wu, Hongge ; Cheng, Jing ; Xiong, Jie
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-390
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info:eu-repo/semantics/article
Description
Abstract
Background. 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.
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circ_0000376 , miR-488-3p , BRD4 , NSCLC , PI3K/PKB
Citation
Histology and Histopathology Vol. 36, nº12 (2021)
URI
http://hdl.handle.net/10201/128146
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Histology and histopathology Vol.36,nº12 (2021)
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