Oncotarget
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2017
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IF 5.168
Hao Gu,Wei Wu,Beilei Yuan,Qiuqin Tang,Dan Guo,Yiqiu Chen,Yankai Xia,Lingqing Hu,Daozhen Chen,Jiahao Sha,Xinru Wang
Genistein (GEN) is one of the isoflavones that has effect on male reproduction. However, the underlying mechanism remains unknown. miRNAs are a type of small non-coding RNAs that play important roles in spermatogenesis. We measured the GEN levels and miR-17-92 cluster expression in infertile subjects and found that miR-17-92 might be involved in GEN induced abnormal spermatogenesis. To clarify, we fed adult ICR mice with different doses of GEN (0, 0.5, 5, 50 and 250 mg/kg/day) for 35 days to study the underlying mechanism. We found that sperm average path velocity, straight-line velocity and eurvilinear velocity of the mice orally with GEN at 5mg/kg/day were significantly decreased, the expression levels of miR-17 and miR-20a in mice testis were higher in corresponding group. We also found miR-20a was the only miRNA that differentially expressed both in human and mice. By applying bioinformatics methods, Limk1 was predicted to be the target gene of miR-20a that is involved in spermatogenesis. Limk1 were significantly decreased in the corresponding group. Dual-luciferase report assay also proved that miR-20a could directly target Limk1. These results implied that Limk1 might be the target gene of miR-20a that is involved in GEN induced abnormal spermatogenesis.
研究领域:
生殖生物学
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分子生物学
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基因组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMISTRY
·
2021
·Vol. 170
·期 3
·349-362
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IF 3.387
Liu Xiaoyu,Guo Bingyan,Zhang Wei,Ma Bocong,Li Yongjun
Diabetic cardiomyopathy (DCM) is a common cardiovascular disease. A declined miR-20a-5p was observed in hearts of diabetic mice, while its effect on DCM remains unknown. Herein, we established streptozotocin-induced DCM rat model and high glucose-stimulated H9C2 model of DCM. Then they were treated with adenovirus expressing miR-20a-5p to explore the function of miR-20a-5p. Insulin tolerance test and intraperitoneal glucose tolerance test assay revealed that miR-20a-5p reduced blood glucose level. Besides, miR-20a-5p improved cardiac dysfunction reflected by reduced heart weight/body weight and left ventricular diastolic pressure, and increased left ventricular systolic pressure and ±LV dp/dt max. MiR-20a-5p prevented cardiomyocyte apoptosis, along with the upregulated c-caspase-3, bax and downregulated bcl-2. Moreover, miR-20a-5p alleviated cardiac hypertrophy as the parameters of atrial natriuretic peptide, B-type natriuretic peptide and MyHC-β decreased. Also, miR-20a-5p attenuated the cardiac fibrosis demonstrated by decreased transforming growth factor-β1, collagen I levels and the inflammatory response manifested by reduced interleukin-6, tumour necrosis factor-α and IL-1β production. Furthermore, miR-20a-5p prevented Jun NH2-terminal kinase (JNK) phosphorylation and nuclear factor-κB (NF-κB) p65nuclear translocation. Similarly, the effects of miR-20a-5p on DCM were confirmed in our in vitro experiments. Additionally, ROCK2 is a possible target gene of miR-20a-5p. ROCK2 overexpression reversed the protective effect of miR-20a-5p on DCM. Overall, miR-20a-5p may effectively ameliorate DCM through improving cardiac metabolism, and subsequently inhibiting inflammation, apoptosis, hypertrophy, fibrosis and JNK/NF-κB pathway via modulating ROCK2.
研究领域:
心脏病学
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分子生物学
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糖尿病
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病理生理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Genetics
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2021
·
IF 4.599
Zhang Jing,Gao Juan,Lin Dengna,Xiong Jing,Wang Jialei,Chen Junfeng,Lin Bingliang,Gao Zhiliang
Acute-on-chronic liver failure (ACLF) is a severe syndrome associated with high mortality. Alterations in the liver microenvironment are one of the vital causes of immune damage and liver dysfunction. Human bone marrow mesenchymal stem cells (hBMSCs) have been reported to alleviate liver injury via exosome-mediated signaling; of note, miRNAs are one of the most important cargoes in exosomes. Importantly, the miRNAs within exosomes in the hepatic microenvironment may mediate the mesenchymal stem cell (MSC)-derived regulation of liver function. This study investigated the hepatocyte exosomal miRNAs which are regulated by MSCs and the target genes which have potential in the treatment of liver failure. Briefly, ACLF was induced in mice using carbon tetrachloride and primary hepatocytes were isolated and co-cultured (or not) with MSCs under serum-free conditions. Exosomes were then collected, and the expression of exosomal miRNAs was assessed using next-generation sequencing; a comparison was performed between liver cells from healthy versus ACLF animals. Additionally, to identify the intracellular targets of exosomal miRNAs in humans, we focused on previously published data, i.e., microarray data and mass spectrometry data in liver samples from ACLF patients. The biological functions and signaling pathways associated with differentially expressed genes were predicted using gene ontology and Kyoto Encyclopedia of Genes and Genomics enrichment analyses; hub genes were also screened based on pathway analysis and the prediction of protein-protein interaction networks. Finally, we constructed the hub gene-miRNA network and performed correlation analysis and qPCR validation. Importantly, our data revealed that MSCs could regulate the miRNA content within exosomes in the hepatic microenvironment. MiR-20a-5p was down-regulated in ACLF hepatocytes and their exosomes, while the levels of chemokine C-X-C Motif Chemokine Ligand 8 (CXCL8; interleukin 8) were increased in hepatocytes. Importantly, co-culture with hBMSCs resulted in up-regulated expression of miR-20a-5p in exosomes and hepatocytes, and down-regulated expression of CXCL8 in hepatocytes. Altogether, our data suggest that the exosomal miR-20a-5p/intracellular CXCL8 axis may play an important role in the reduction of liver inflammation in ACLF in the context of MSC-based therapies and highlights CXCL8 as a potential target for alleviating liver injury.
研究领域:
肝病学
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干细胞生物学
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分子生物学
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基因组学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
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IF 5.6
Jing Zhang,Juan Gao,Xianlong Li,Dengna Lin,Zhihui Li,Jialei Wang,Junfeng Chen,Zhiliang Gao,Bingliang Lin
Balancing hepatocyte death and proliferation is key to non-transplantation treatments for acute liver failure (ALF), which has a high short-term mortality rate. Small extracellular vesicles (sEVs) may act as mediators in the repair of damaged liver tissue by mesenchymal stem cells (MSCs). We aimed to investigate the efficacy of human bone marrow MSC-derived sEVs (BMSC-sEVs) in treating mice with ALF and the molecular mechanisms involved in regulating hepatocyte proliferation and apoptosis. Small EVs and sEV-free BMSC concentrated medium were injected into mice with LPS/D-GalN-induced ALF to assess survival, changes in serology, liver pathology, and apoptosis and proliferation in different phases. The results were further verified in vitro in L-02 cells with hydrogen peroxide injury. BMSC-sEV-treated mice with ALF had higher 24 h survival rates and more significant reductions in liver injury than mice treated with sEV-free concentrated medium. BMSC-sEVs reduced hepatocyte apoptosis and promoted cell proliferation by upregulating miR-20a-5p, which targeted the PTEN/AKT signaling pathway. Additionally, BMSC-sEVs upregulated the mir-20a precursor in hepatocytes. The application of BMSC-sEVs showed a positive impact by preventing the development of ALF, and may serve as a promising strategy for promoting ALF liver regeneration. miR-20a-5p plays an important role in liver protection from ALF by BMSC-sEVs.
研究领域:
干细胞生物学
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分子生物学
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肝病学
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再生医学
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DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2023
·
IF 3.7
Heyang Zhang,Yuan Tao,Xin Ding,Yue Wang,Xiaoxue Wang
Acute myeloid leukemia (AML) is a myeloid malignancy with generally high mortality. Although recent advances in AML research have revealed that circRNAs play significant roles in AML progression, our understanding of the leukemogenic mechanism of circRNAs remains very limited. In this study, increased expression of hsa_circ_0013880 was observed in bone marrow mononuclear cells (BMNCs) of AML patients. Overexpression of hsa_circ_0013880 promotes AML cell proliferation and migration and reduces cell apoptosis. Mechanistically, hsa_circ_0013880 could elevate the expression of USP32, a deubiquitinating enzyme that is highly expressed in the BMNCs of AML patients. Given the deubiquitination function of USP32, we further hypothesize that USP32 may mediate the malignant behaviors of AML cells by regulating the stability of Ras-related protein (Rap1b). At the molecular level, we find that silencing of USP32 increases ubiquitinated Rap1b. Overexpression of Rap1b restores the effects of USP32 knockdown, which further verifies our hypothesis. In addition, we propose another hypothesis that a potential regulatory network among hsa_circ_0013880, miR-148a-3p/miR-20a-5p and USP32 might exist in the development of AML, according to bioinformatics website predictions and our preliminary experimental verification. Overall, our findings will enrich the understanding of the hsa_circ_0013880/USP32/Rap1b axis in AML development, which may contribute to the development of novel therapeutic strategies for AML.
研究领域:
肿瘤学
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分子生物学
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血液学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
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