Xiaohua Li1, Shuhong Yi2, Yinan Deng1, Jintao Cheng1, Xiaocai Wu1, Wei Liu1, Yan Tai3, Guihua Chen1, Qi Zhang1, Yang Yang4. 1. Liver Surgery Center, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China. 2. Liver Surgery Center, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 3. Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China. 4. Liver Surgery Center, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China. Electronic address: yysysu@163.com.
Abstract
BACKGROUND: Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgeons. Because microRNAs (miRNAs) participate in various hepatic pathophysiological processes, this study aimed to explore the role and potential mechanism of miR-124 in hepatic IRI. METHODS: A liver IRI model was established in rats. The differential expression of miRNAs was detected using microarrays, and the expression of miR-124 was measured by qRT-PCR. A hydrogen peroxide (H2O2)-induced oxidative stress apoptosis model was also established. Cell apoptosis was detected by flow cytometry, and viability was detected by CCK8. The expression of Rab38 was detected by Western blotting and qRT-PCR, and a luciferase reporter assay was used to verify the expression of the miR-124 target gene. RESULTS: The miRNA spectrum changes dramatically after hepatic IRI in rats, and miR-124 is significantly down-regulated after liver IRI. MiR-124 decreases the H2O2-induced apoptosis of human hepatic L02 cells by up-regulating the activation of the AKT pathway. Rab38 is a target gene of miR-124 and is involved in H2O2-induced apoptosis. Interference with the expression of the Rab38 gene can protect hepatic L02 from H2O2-induced apoptosis by increasing the phosphorylation of AKT. These protective effects of miR-124 are attenuated by over-expression of Rab38. CONCLUSIONS: Many miRNAs are involved in hepatic IRI in rats, and miR-124 is significantly decreased in this model. MiR-124 significantly decreases the H2O2-induced apoptosis of human hepatic L02 cells by targeting the Rab38 gene and activating the AKT pathway.
BACKGROUND:Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgeons. Because microRNAs (miRNAs) participate in various hepatic pathophysiological processes, this study aimed to explore the role and potential mechanism of miR-124 in hepatic IRI. METHODS: A liver IRI model was established in rats. The differential expression of miRNAs was detected using microarrays, and the expression of miR-124 was measured by qRT-PCR. A hydrogen peroxide (H2O2)-induced oxidative stress apoptosis model was also established. Cell apoptosis was detected by flow cytometry, and viability was detected by CCK8. The expression of Rab38 was detected by Western blotting and qRT-PCR, and a luciferase reporter assay was used to verify the expression of the miR-124 target gene. RESULTS: The miRNA spectrum changes dramatically after hepatic IRI in rats, and miR-124 is significantly down-regulated after liver IRI. MiR-124 decreases the H2O2-induced apoptosis of human hepatic L02 cells by up-regulating the activation of the AKT pathway. Rab38 is a target gene of miR-124 and is involved in H2O2-induced apoptosis. Interference with the expression of the Rab38 gene can protect hepatic L02 from H2O2-induced apoptosis by increasing the phosphorylation of AKT. These protective effects of miR-124 are attenuated by over-expression of Rab38. CONCLUSIONS: Many miRNAs are involved in hepatic IRI in rats, and miR-124 is significantly decreased in this model. MiR-124 significantly decreases the H2O2-induced apoptosis of human hepatic L02 cells by targeting the Rab38 gene and activating the AKT pathway.