ONCOLOGY REPORTS
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2019
·Vol. 42
·期 1
·313-320
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IF 3.041
Xuan‑Chen Tao,Xin‑Yu Zhang,Shi‑Bo Sun,De‑Quan Wu
MicroRNAs (miRNAs) are a class of short noncoding RNAs that negatively regulate gene expression and act as oncogenes or tumor suppressors. Numerous miRNAs have been reported be associated with the occurrence and development of gastric carcinoma (GC). For instance, miR‑92a has been observed to be overexpressed in GC; however, the precise mechanisms underlying the role of miR‑92a in GC and its role in clinical therapy require further investigation. In the present study, it was reported that miR‑92a expression was significantly upregulated in GC tissues compared with in adjacent tissues. Additionally, suppression of miR‑92a significantly reduced SGC7901 cell viability as demonstrated by a Cell Counting Kit‑8 and colony formation assays. Suppression of miR‑92a inhibited SGC7901 cell proliferation as determined by Ki‑67 immunofluorescence staining, and the expression levels of proliferating cell nuclear antigen, cyclin dependent kinase (CDK)4 and CDK6, and increased that of p53. In addition, we reported that suppression of miR‑92a induced apoptosis in SGC7901 cells. Furthermore, bioinformatics analysis identified that ING2 as a potential target of miR‑92a. Downregulation of miR‑92a significantly increased ING2 expression at the mRNA and protein levels. A dual‑luciferase reporter assay validated a direct binding site of miR‑92a on ING2. In addition, SGC7901 cells with suppression of miR‑92a were more sensitive to doxorubicin treatment. Knockdown of miR‑92a reduced the half‑maximal inhibitory concentration of doxorubicin from 147.6 nM to 82.1 nM in SGC7901 cells. Knockdown of miR‑92a also reduced SGC7901 cell survival under doxorubicin stimulation. Furthermore, SGC7901 cells with suppression of miR‑92a harbored a greater number of DNA damage foci upon doxorubicin treatment compared with in control cells. The findings of the present study revealed that miR‑92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in GC cells, which suggests a potential therapeutic strategy for the treatment of GC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Ning Xu,Guanzheng Cui,Shengyin Zhao,Yu Li,Qian Liu,Xuchang Liu,Chuanliang Zhao,Rongjie Feng,Mingjie Kuang,Shijie Han
Introduction Osteoporosis is a common bone disease in which the bone loses density and strength and is prone to fracture. Bone marrow mesenchymal stem cells (BMSCs) are important in bone-related diseases. Exosomes, as mediators of cell communication, have potential in cell processes. Previous studies have focused on muscle factors’ regulation of bone remodeling, but research on exosomes is lacking.Methods In order to confirm the therapeutic effect of mechanically stimulated myocytes (C2C12) derived exosomes (Exosome-MS) on the Glucocorticoid-induced osteoporosis(GIOP) compared with unmechanically stimulated myocytes (C2C12) derived exosomes (Exosomes), we established a dexamethasone-induced osteoporosis model in vivo and in vitro. Cell viability and proliferation were assessed using CCK8 and EDU assays. Osteogenic potential was evaluated through Western blotting, real-time PCR, alkaline phosphatase activity assay, and alizarin red staining. Differential expression of miRNAs was determined by high-throughput sequencing. The regulatory mechanism of miR-92a-3p on cell proliferation and osteogenic differentiation via the PTEN/AKT pathway was investigated using real-time PCR, luciferase reporter gene assay, Western blotting, and immunofluorescence. The therapeutic effects of exosomes were evaluated in vivo using microCT, HE staining, Masson staining, and immunohistochemistry.Results In this study, we found that exosomes derived from mechanical stress had a positive impact on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). Importantly, we demonstrated that miR-92a-3p mimics could reverse dexamethasone-induced osteoporosis in vitro and in vivo, indicating that mechanical stress-induced mouse myoblast-derived exosomes could promote osteogenesis and prevent the occurrence and progression of osteoporosis in mice through miR-92a-3p/PTEN/AKT signaling pathway.Conclusion Exosomes derived from mechanical stress-induced myoblasts can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through miR-92a-3p/PTEN/AKT signaling pathway, and can have a therapeutic effect on glucocorticoid-induced osteoporosis in mice in vivo.
研究领域:
骨科
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细胞生物学
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分子生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
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2023
·
IF 3.8
Xiao Ji,Zhenwu Zhao
Background Silencing of miR-92a-3p may be beneficial in relieving depression of chronically stressed rats. The level of kruppel-like factor 2 (KLF2) was increased in the striatum of depressed rats after ketamine treatment. Enriched environment (EE) ameliorated depression-like behaviors in rats. However, the specific mechanism of EE treatment on depression induced by chronic unpredictable mild stress (CUMS) remains unclear. Methods After CUMS-induced male Sprague Dawley rats were treated under EE or/and Adeno-Associated Virus (AAV)-miR-92a-3p, depression-like behaviors, cognitive ability, dendritic spine density, as well as levels of miR-92a-3p and KLF2 were detected by the behavioral tests, morris water maze test, Golgi staining, and quantitative real-time polymerase chain reaction (qRT-PCR) as needed. The body weight of rats was also measured. Next, primary hippocampal neurons were cultivated. The targeting relationship between miR-92a-3p and KLF2 was analyzed by TargetScan v7.2 and dual-luciferase reporter assay. After hippocampal neurons were transfected with miR-92a-3p mimic or/and overexpressed KLF2 vector, the cell viability, and apoptosis, together with the levels of KLF2, brain-derived neurotrophic factor (BDNF), phosphorylated (p)-tropomysin related kinase B (p-TrkB) and TrkB were determined by MTT assay, flow cytometry, qRT-PCR, and western blot as needed. Results EE ameliorated CUMS-induced depression-like behaviors and cognitive ability, and elevated the neuronal dendritic spine density and KLF2 level, but reduced miR-92a-3p level in hippocampal tissues, while the above effects were reversed by AAV-miR-92a-3p. MiR-92a-3p mimic restrained cell viability, along with p-TrkB/ TrkB and BDNF levels, but promoted apoptosis in hippocampal neurons, which were reversed by overexpressed KLF2. Conclusion EE ameliorates CUMS-induced depression-like symptoms in rats via regulating the miR-92a-3p/KLF2 pathway.
研究领域:
神经科学
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分子生物学
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行为科学
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药理学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Luhai Wang,Nana Wang,Lin Deng,Chao Min,Yi Kang,Tingting Bai,Guodong Zhao,Mengdong Yang,Yefei Zhu,Yu Zhang
Simultaneous analysis of multiple protein and nucleic acid biomarkers in one clinical sample can provide clinically valuable results for the diagnosis, monitoring, and management of diseases. However, current diagnostic platforms primarily rely on the independent detection of proteins and nucleic acids, which is time-consuming and labor-intensive. In this study, we propose a microfluidic chip system that integrates microfluidic molecular Point-of-Care Testing (POCT) technology and microfluidic homogeneous chemiluminescence analysis (CLIA) technology for simultaneous detection of protein and nucleic acid biomarkers of ovarian cancer (OC). The integrated system shows good detection limits of 10 fM for miR-92a and 15 pM for HE4. In primary clinical tests with human samples, the diagnostic sensitivity and specificity of the simultaneous detection of two biomarkers (miR-92a and HE4) for OC were 100 % and 96.1 %, respectively, and the area under the curve (AUC) was 0.996. Therefore, the combined evaluation of multiple biomarkers of different dimensions can improve the specificity and sensitivity of diagnosis. This system can also be applied to other tumor markers and biomarkers in other fields of diseases, offering a broad spectrum of diagnostic capabilities.
研究领域:
医学诊断
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分子生物学
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产品关联
DOI
高影响因子
ACS Omega
·
2025
·
IF 4.3
Bin Wang,Peng He,Xiaowei Liu,Shunjie Wu,Xinlin Lu,Bin Xu
Muscles and bones are adjacent in spatial position and closely related in function. Exosomes can achieve communication between donor and receptor cells by carrying molecules, such as miRNAs. Therefore, the purpose of this study is to use exosome-miRNA as a bridge, explore the correlation between clinical manifestations, and use bioinformatics and machine learning to cluster and screen exosome-miRNA sequencing data. In vitro and in vivo experiments were conducted to validate the screened molecules. Three parts were explored to identify miRNAs that play a key regulatory role in the muscle–exosome–bone system. Ultimately, it was found that miR-92a-1-5p may play a crucial role in this system; that is, atrophic muscle cells can inhibit osteogenic differentiation by releasing exosomes carrying miR-92a-1-5p into osteoblasts and targeting Col1a1.
研究领域:
生物信息学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR BIOCHEMISTRY
·
2023
·Vol. 124
·期 4
·557-572
·
IF 4
Juan Gu,Xu Chu,Yujia Huo,Chaoyi Liu,Qingge Chen,Shengnan Hu,Yanyan Pei,Pu Ding,Sen Pang,Ming Wang
Gastric cancer (GC) with pulmonary metastasis is one of the deadliest diseases in the world; however, the underlying pathological mechanisms and potential therapeutic targets remain to be elucidated. As exosomes play indispensable roles in the formation of premetastatic niches (PMN) and cancer metastasis. Therefore, investigating the underlying mechanisms of exosome-mediated pulmonary metastasis of GC may shed new light on identifying novel therapeutic targets for GC treatment. GC-derived exosomes were isolated from the conditioned medium of mouse forestomach carcinoma (MFC) cell line. The effects of MFC-derived exosomes on pulmonary macrophage polarization were analyzed by reverse- transcription polymerase chain reaction and flow cytometry. Expression of PD-L1 and other proteins was evaluated by Western blot. Exosomal microRNAs (miRNAs) were analyzed by microarray. GC-derived exosomes (GC-exo) accumulated in high numbers in the lungs and were ingested by macrophages. The extracellular-signal-regulated kinase (ERK) signaling pathway was activated by GC-exo, inducing macrophage immunosuppressive-phenotype differentiation and increased PD-L1 expression. miRNA-sequencing identified 130 enriched miRNAs in GC-exo. Among the enriched miRNAs, miR-92a-3p plays a major role in activating ERK signaling via inhibition of PTEN expression. In addition, inhibiting ERK signaling with PD98059 significantly reduced the expression of PD-L1 in macrophages and, therefore, reversed the immunosuppressive PMN and inhibited the colonization of GC cells in the lungs. This study identified a novel mechanism of GC-exo mediated PD-L1 expression in lung macrophages that facilitates lung PMN formation and GC pulmonary metastasis, which also provided a potential therapeutic target for GC with pulmonary metastasis treatment.
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症生物学
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DOI
PubMed
高影响因子
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