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microRNA-4331 promotes TGEV-induced mitochondrial damage via targeting RB1, up-regulating IL1RAP, and activating p38 MAPK pathway in vitro.

microRNA-4331 promotes TGEV-induced mitochondrial damage via targeting RB1, up-regulating IL1RAP, and activating p38 MAPK pathway in vitro.
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Zhao X, Bai X, Guan L, Li J, Song X, Ma X, Guo J, Zhang Z, Du Q, Huang Y, Tong D,


Zhao X, Bai X, Guan L, Li J, Song X, Ma X, Guo J, Zhang Z, Du Q, Huang Y, Tong D, (click to view)

Zhao X, Bai X, Guan L, Li J, Song X, Ma X, Guo J, Zhang Z, Du Q, Huang Y, Tong D,

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Molecular & cellular proteomics : MCP 2017 12 07() pii mcp.RA117.000432
Abstract

Transmissible gastroenteritis virus (TGEV), a member of the coronaviridae family, could cause fatal diarrhea of piglets and result in numerous economic losses. Previous studies demonstrated that TGEV infection could lead to mitochondrial damage and up-regulate miR-4331 level. So miR-4331 may play an important regulatory role in the control of mitochondrial function. To explore the potential role of miR-4331 in mitochondrial damage, we adopted a strategy consisting of quantitative proteomic analysis of porcine kidney (PK-15) cells in response to miR-4331 and TGEV infection. Eventually, 69 differentially expressed proteins were gained. The target of miR-4331 was identified. The effects of miR-4331 and its target RB1 on mitochondrial Ca2+ level, mitochondrial membrane potential (MMP), interleukin-1 receptor accessory protein (IL1RAP), p38 MAPK signaling pathway were investigated. The results showed that miR-4331 elevated mitochondrial Ca2+ level, reduced MMP, targets Retinoblastoma 1 (RB1), up-regulated IL1RAP, and induced activation of p38 MAPK pathway during TGEV infection. RB1 was identified as the direct targets of miR-4331 and down-regulated IL1RAP, suppressed the activation of p38 MPAK, and attenuated TGEV-induced mitochondrial damage. In addition, IL1RAP played a positive role in activating p38 MAPK signaling and negative role in TGEV-induced mitochondrial damage. The data indicate that miR-4331 aggravates TGEV-induced mitochondrial damage by repressing expression of RB1, promoting IL1RAP, and activating p38 MAPK pathway.

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