USF-1 inhibition protects against oxygen-and-glucose-deprivation-induced apoptosis via the downregulation of miR-132 in HepG2 cells

•Knockdown of USF-1 protected the HepG2 cells from oxygen and glucose deprivation (OGD)-induced apoptosis.•A set of miRNAs were deregulated in the HepG2 cells with USF-1 siRNA treatment.•miR-132 could inhibit the protective roles of USF-1 siRNA in the OGD-induced apoptosis in HepG2 cells.•USF-1 coul...

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Published in:Biochemical and biophysical research communications Vol. 446; no. 4; pp. 1053 - 1059
Main Authors: Wang, Renjie, Liang, Haiqian, Li, Hui, Dou, Herong, Zhang, Minghua, Baobuhe, Du, Zhenhua, Gao, Mojie, Wang, Ruimin
Format: Journal Article
Language:English
Published: United States Elsevier Inc 18-04-2014
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Summary:•Knockdown of USF-1 protected the HepG2 cells from oxygen and glucose deprivation (OGD)-induced apoptosis.•A set of miRNAs were deregulated in the HepG2 cells with USF-1 siRNA treatment.•miR-132 could inhibit the protective roles of USF-1 siRNA in the OGD-induced apoptosis in HepG2 cells.•USF-1 could regulate miR-132 expression in HepG2 cells.•An axis of USF-1/miR-132 inhibited OGD-induced apoptosis in HepG2 cells. Upstream stimulatory factor 1 (USF-1) is an important transcription factor that participates in glucose metabolism and tumorigenesis. The aim of the current study was to explore the regulatory mechanism of USF-1 in HepG2 cells exposed to oxygen and glucose deprivation (OGD). After the establishment of the OGD model in HepG2 cells, we determined that the cells treated with OGD exhibited a high apoptotic rate and that the introduction of siRNA against USF-1 protected the cells from OGD-induced apoptosis. The miRNA microarray results demonstrated that a set of miRNAs were deregulated in the cells transfected with USF-1 siRNA, and the set of downregulated miRNAs included a novel miRNA, miR-132. Further analyses indicated that miR-132 overexpression inhibits the protective roles of USF-1 siRNA in OGD-induced apoptosis. We also identified several binding sites for USF-1 in the miR-132 promoter. The silencing of USF-1 resulted in a reduction in miR-132 expression, and USF-1 overexpression increased the expression of this miRNA. Our study indicated that the silencing of USF-1 plays protective roles in OGD-induced apoptosis through the downregulation of miR-132, which indicates that the silencing of USF-1 may be a therapeutic strategy for the promotion of cancer cell survival under OGD conditions.
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ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2014.03.064