CHEMICAL RESEARCH IN TOXICOLOGY
·
2025
·
IF 3.8
Xiaomin Ye,Peiqu Zhong,Qiongfang Chen,Dongmei Zhou,Jieyu Luo,Youcai Liang,Jiayuan Zhang,Lijian Zhao
The widespread use of perfluorooctanesulfonic acid (PFOS) has raised concerns regarding its potential on pregnant women, particularly in relation to the development of pre-eclampsia (PE). This study investigates the impact of PFOS exposure on the LncRNA/Rnd3 axis in pregnant mice and its association with trophoblast cell functions in PE. Bioinformatics analysis revealed PFOS-related gene alterations in PE, with pathways enriched in apoptotic signaling and cytokine interactions. Experimental findings showed the downregulation of Oip5os1 and Rnd3, along with the upregulation of miR-155, affecting trophoblast behavior. Animal experiments confirmed that PFOS-induced gene expression changes are linked to PE progression. PFOS exposure impairs trophoblast proliferation and migration via the Oip5os1/miR-155/Rnd3 axis, contributing to PE development.
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Fangling Li,Dongdong Cao,Lixia Yao,Wenyi Gu,Zhiyong Liu,Dongmei Li,Lin Cui
Kaposi’s sarcoma-associated herpesvirus (KSHV) can infect a variety of cells and cause malignant tumors. At present, the use of microRNA (miRNA) for anti-KSHV is a promising treatment strategy, but the instability and non-specific uptake of miRNA still limit its use in the treatment of KSHV. In the present study, we constructed a nano-drug delivery system employing chemical grafting and electrostatic adsorption to solve the problems of easy degradation and low cell uptake of miRNA during direct administration. This nano-drug delivery system is to graft 4-carboxyphenylboric acid (PBA) and lauric acid (LA) onto polyethylenimine (PEI) through amidation reaction, and then prepare cationic copolymer nanocarriers (LA-PEI-PBA). The drug-carrying nanocomplex LA-PEI-PBA/miR-34a-5p was formed after further electrostatic adsorption of miR-34a-5p on the carrier and could protect miR-34a-5p from nuclease and serum degradation. Modification of the drug-carrying nanocomplex LA-PEI-PBA/miR-34a-5p by targeted molecule PBA showed effective uptake, increase in the level of miR-34a-5p, and inhibition of cell proliferation and migration in KSHV-infected cells. In addition, the drug-carrying nanocomplex could also significantly reduce the expression of KSHV lytic and latent genes, achieving the purpose of anti-KSHV treatment. In conclusion, these cationic copolymer nanocarriers with PBA targeting possess potential applications in nucleic acid delivery and anti-KSHV therapy.
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Qianlong Wang,Lancong Liu,Xiaoyi Chen,Tiantian Wang,Hua Zhou,Hui Huang,Linsen Qing,Pei Luo
Urine is the most appropriate body fluid for analysis because it is easily and less-invasively obtained than blood; thus, urinary miRNAs can better represent the local stage of the disease and might grow up to be a new class of noninvasive biomarkers of postmyocardial infarction (MI). Monofunctionalized Au nanoparticles (AuNPs) with only one selective DNA at a specific location are more promising in nanotechnology. This study developed a urinary miRNA ultratrace detection strategy based on single-target DNA-functionalized AuNPs for the noninvasive prognosis of post-MI. The AuNPs were designed with only single-stranded biotinylated DNA complementary to the target miRNA through a ratio-optimized stoichiometric method for the first time. Combined with the duplex specific nuclease-assisted target recycling amplification, the single-target DNA-functionalized AuNPs for the first time were used in inductively coupled plasma–mass spectrometry for the determination of urinary miRNA with high sensitivity. After optimizing the reaction conditions, a linear detection range between 1 fM and 10 pM for miR-155 and a detection limit of 0.47 fM were obtained. Finally, the target miR-155 in urine samples collected from MI rats was quantified and the level of miR-155 in MI groups was 30 times higher than in the control groups. The results suggest that urinary miR-155 could be a novel biomarker for the noninvasive diagnosis of MI.
研究领域:
分子生物学
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纳米医学
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临床诊断学
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DOI
PubMed
高影响因子
NEUROMOLECULAR MEDICINE
·
2021
·Vol. 24
·期 2
·224-231
·
IF 3.843
Wei Guangxin,Li Shengjun,Wang Pengcheng,Wang Shouxian,Zhao Yujing
Glioma is a kind of brain tumor with low overall survival and treatment success rates in the advanced stage. Evidence has shown microRNA-575 (miR-575) plays an important role in the generation and development of various cancers. This study aimed to explore the function of miR-575 in the prognosis and cell biological behavior of glioma. qRT-PCR was used to evaluate the expression of miR-575 in glioma tissues and cells, Kaplan–Meier survival analysis and Cox regression analysis were used to evaluate the prognostic value. The proliferation ability of glioma cells was determined by MTT assay; the invasion and migration abilities were determined by transwell assays. Compared with normal brain tissues, the expression of miR-575 in glioma tissue cells was significantly up-regulated ( P < 0.001). The survival rate of patients in the miR-575 high expression group was significantly lower than that in the low expression group ( P = 0.020). In addition, the overexpression of miR-575 promoted the proliferation, migration, and invasion of glioma cells. The results of this study suggested that miR-575 may be a new biomarker for the prognosis of glioma.
研究领域:
肿瘤学
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分子生物学
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神经科学
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DOI
PubMed
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Yaru Wang,Yanting Li,Xin Li
Background This study compared the effect of ultrasound microbubble-mediated miR-503–5p downregulation with that of pure liposome-mediated miR-503–5p downregulation on colorectal cancer (CRC) progression and explored the downstream mechanism. Methods Bioinformatics tools were utilized to predict miR-503–5p-targeted genes and CRC progression-associated genes. MiR-503–5p and sal-like 1 (SALL1) expressions in CRC cells and tissues were analyzed by qRT-PCR and/or bioinformatics tools; their correlations with overall survival and clinicopathological features of CRC patients were presented, and their interaction was validated by dual-luciferase reporter assay. CRC cells received ultrasound microbubble-mediated miR-503–5p downregulation and/or liposome-mediated miR-503–5p downregulation or SALL1 silencing. Cell phenotype changes were evaluated by flow cytometry, as well as MTT, Wound healing, Transwell and tube formation assays. E-cadherin, N-cadherin, Vimentin , B-cell lymphoma (Bcl)− 2, Cleaved caspase-3, and SALL1 expressions in cells were analyzed by Western blot . Results Upregulated miR-503–5p in CRC tissues and cells was detected, associated with poorer cell differentiation , easier lymph node metastasis and higher TNM stages, and related to poorer prognoses of CRC patients. Ultrasound microbubble-mediated miR-503–5p downregulation relative to pure liposome-mediated miR-503–5p downregulation better decreased viability, inhibited migration, invasion and tube formation, enhanced apoptosis, upregulated SALL1, E-cadherin and Cleaved caspase-3, and downregulated miR-503–5p, N-cadherin, Vimentin and Bcl-2 in CRC cells. SALL1 was targeted by miR-503–5p, low-expressed in CRC tissues and cells and positively related to CRC patients’ survival. Silencing SALL1 exerted the opposite effects, which reversed the effects of ultrasound microbubble-mediated miR-503–5p downregulation and vice versa. Conclusion Ultrasound microbubble-mediated miR-503–5p downregulation suppressed in vitro CRC progression via promoting SALL1 expression.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
CYTOTECHNOLOGY
·
2021
·Vol. 73
·期 3
·483-496
·
IF 2.058
Lu Hengxiao,Wang Hao,Sun Peidao,Wang Jiang,Li Shuhai,Xu Tongzhen
We investigated the role of miR-522-3p in thymoma-associated myasthenia gravis (TAMG), and the mechanism of action in T cells. The miR-522-3p expression in normal serum, non-thymoma MG patient serum and TAMG patient serum and tissues was detected by quantitative real-time PCR (qRT-PCR), respectively. We assessed miR-522-3p expression in Jurkat cells and human CD4 + T cells after activation by anti-CD3 and anti-CD28 using qRT-PCR. The viability, proliferation, cycle distribution and the levels of CD25, CD69, interleukin-2 (IL-2) and IL-10 in transfected Jurkat cells were detected by Cell counting kit-8, 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, qRT-PCR, respectively. Targeting relationships of miR-522-3p and SLC31A1 were predicted and validated by bioinformatics analysis and dual-luciferase reporter. The viability, proliferation, cycle distribution and the levels of SLC31A1, CD25, CD69, IL-2 and IL-10 in transfected Jurkat cells were detected by above methods and western blot. The miR-522-3p expression was declined in TAMG and activated T cells. MiR-522-3p inhibitor promoted cell viability, EdU positive cells, cycle progression, and the level of CD25, CD69, IL-2 and IL-10 in Jurkat cells, while the effect of miR-522-3p mimic was the opposite. SLC31A1 was targeted by miR-522-3p, and miR-522-3p inhibited SLC31A1 expression. Overexpressed SLC31A1 reversed the inhibitory effects of miR-522-3p mimic on cell viability, EdU positive cell, cycle progression, and the levels of IL-2 and IL-10 in transfected Jurkat cells. MiR-522-3p expression was down-regulated in TAMG, and miR-522-3p inhibited proliferation and activation by regulating SLC31A1 expression in T cells.
研究领域:
分子生物学
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免疫学
·
医学遗传学
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DOI
PubMed
高影响因子
Clinical Interventions in Aging
·
2021
·
IF 4.458
Junyang Chen,Xuefeng Li,Feng Zhao,Yubo Hu
Background Propofol (PPF) ameliorates ischemia/reperfusion (I/R) injury in multiple organs by reducing apoptosis and release of pro-inflammatory cytokines. This study aims to explore the mechanism of PPF in attenuating myocardial ischemia-reperfusion injury (MIRI). Materials and Methods Rat MIRI model was established, and PPF pre-treatment was performed 10 min before I/R. H9c2 cardiomyocytes treated with hypoxia/reoxygenation (H/R) were used to establish an in vitro model. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate HOTAIR and miR-17-5p expression levels. Flow cytometry was employed to detect the apoptosis of H9c2 cells. The interaction between HOTAIR and miR-17-5p was determined by bioinformatics analysis, luciferase reporter gene analysis, and RNA immunoprecipitation experiments. STAT3 and p-STAT3 expressions were detected by Western blot. Results PPF pre-treatment significantly reduced creatine kinase isoenzyme (CK-MB) and serum lactate dehydrogenase (LDH) levels in the serum of the rats with MIRI. PPF pre-treatment remarkably up-regulated HOTAIR expression and down-regulated miR-17-5p expression in both in vivo and in vitro models. HOTAIR adsorbed miR-17-5p to repress the expression of miR-17-5p. PPF pre-treatment markedly inhibited cardiomyocyte apoptosis induced by I/R or H/R. HOTAIR knockdown could partially reverse the protective effects of PPF on MIRI. HOTAIR could activate STAT3 signaling via repressing miR-17-5p expression. Conclusion PPF protects the MIRI by modulating the HOTAIR/miR-17-5p/STAT3 axis.
研究领域:
药理学
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心脏病学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
Immunity Inflammation and Disease
·
2023
·Vol. 11
·期 5
·e814
·
IF 3.2
Hecheng Wang,Jiadan Teng,Mingtao Wang,Yuhang Zhang,Xiaoshuang Liu,Zhuya Liu
Background Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been reported to play regulatory roles in ulcerative colitis (UC). In this study, we aimed to determine the specific roles and action mechanism of the nuclear paraspeckle assembly transcript 1 ( NEAT1 ) in UC. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the lncRNA NEAT1 and miR-493-5p expression levels in patients with UC and healthy volunteers. We determine the forecast linkage points of NEAT1 and miR-493-5p using Starbase and those of miR-493-5p and Rab27A using TargetScan, and further verified them using a double luciferase gene reporter kit. RT-qPCR and Western blot analysis were used to determine the lncRNA NEAT1 , miR-493-5p , and Rab27A expression levels in lipopolysaccharide (LPS)-induced Caco-2 cells. Flow cytometry and cell counting kit-8 were used to assess Caco-2 cell viability. Tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-1β levels were determined via an enzyme-linked immunosorbent assay. Results Expression levels of NEAT1 were upregulated and those of miR-493-5p were downregualted in 10 ng/mL LPS-treated Caco-2 cells and patients with UC. Dual-luciferase gene reporter assay revealed that miR-493-5p is linked to NEAT1 , and Rab27A is a downstream target of miR-493-5p . Overexpression of miR-493- 5p inhibited the apoptosis and inflammation in LPS-treated Caco-2 cells. Moreover, downregulation of lncRNA NEAT1 expression also inhibited the apoptosis and inflammation in LPS-treated Caco-2 cells, which was reversed by Rab27A plasmid cotransfection. Conclusion Our results revealed that NEAT1 participates in UC progression by inhibiting miR-493-5p expression.
研究领域:
分子生物学
·
胃肠病学
·
免疫学
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DOI
PubMed
高影响因子
Genes & Diseases
·
2020
·
IF 4.803
YongSheng Zhang,YiLong Yao,ZiShuai Wang,Dan Lu,YuanYuan Zhang,Adeyinka Abiola Adetula,SiYuan Liu,Min Zhu,YaLan Yang,XinHao Fan,MuYa Chen,YiJie Tang,Yun Chen,YuWen Liu,GuoQiang Yi,ZhongLin Tang
The microRNAs (miRNAs) play an important role in regulating myogenesis by targeting mRNA. However, the understanding of miRNAs in skeletal muscle development and diseases is unclear. In this study, we firstly performed the transcriptome profiling in differentiating C2C12 myoblast cells. Totally, we identified 187 miRNAs and 4260 mRNAs significantly differentially expressed that were involved in myoblast differentiation. We carried out validation of microarray data based on 5 mRNAs and 5 miRNAs differentially expressed and got a consistent result. Then we constructed and validated the significantly up- and down-regulated mRNA-miRNA interaction networks. Four interaction pairs (miR-145a-5p- Fscn1, miR-200c-5p- Tmigd1, miR-27a-5p- Sln and miR-743a-5p- Mob1b ) with targeted relationships in differentiated myoblast cells were demonstrated. They are all closely related to myoblast development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated cell cycle signals important for exploring skeletal muscle development and disease. Functionally, we discovered that miR-743a targeting gene Mps One Binder Kinase Activator-Like 1B ( Mob1b ) gene in differentiated C2C12. The up-regulated miR-743a can promote the differentiation of C2C12 myoblast. While the down-regulated Mob1b plays a negative role in differentiation. In addition, the expression profile of miR-743a and Mob1b are consistent with skeletal muscle recovery after Cardiotoxin (CTX) injury. Our study revealed that miR-743a-5p regulates myoblast differentiation by targeting Mob1b involved in skeletal muscle development and regeneration. Our findings made a further exploration for mechanisms in myogenesis and might provide potential possible miRNA-based target therapies for skeletal muscle regeneration and disease in the near future.
研究领域:
分子生物学
·
肌肉发育
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再生医学
·
基因调控
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
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2022
·
IF 5.763
Min Li,Yanyan Yang,Jinbao Zong,Zhibin Wang,Shaoyan Jiang,Xiuxiu Fu,Xiangqin He,Xiaoxin Li,Qianqian Xue,Jian-Xun Wang,Tao Yu
Background Aortic dissection (AD) is a lethal cardiac disorder and one of the most concerning cardiovascular diseases (CVDs). Increasing evidence indicates that human aortic vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of AD, especially related to phenotypic transformation. And notablely, the development of AD is also accompanied by inflammation. Methods By using quantitative real-time PCR and fluorescence in situ hybridization (FISH), we detected the expression levels of miR-564 in vitro and in vivo. The effects of miR-564 proliferation and migration were investigated in VSMCs. The downstream targets of miR-564 were found by bioinformatics analyse, and verified in the regulation on VSMCs. An AD murine model was constructed and clinical evaluation was performed to explore the critical roles of miR-564 in vivo. At the same time, the level of inflammation was detected using quantitative real-time PCR and immunofluorescence. Results Overexpression of miR-564 inhibited cell proliferation and migration, as well as phenotype switch, with or without platelet-derived growth factor BB (PDGF-BB) treatment, whereas downregulation of miR-564 led to opposite results. Mechanistically, miR-564 directly interacted with the target genes proto-oncogene (SKI) and neurogranin (NRGN) to regulate the biological functions of VSMCs. In particular, animal experiments demonstrated that miR-564 can alleviate the progression of AD mainly through mediating phenotypic swithing and inflammation which was consistent with clinical evaluation. Conclusions Our study identified miR-564 as a significant molecule that attenuates AD progression by inhibiting inflammation and VSMCs proliferation, migration and phenotypic transformation, suggesting that it may be a potential therapeutic target for AD.
研究领域:
心血管疾病
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分子生物学
·
病理学
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DOI
PubMed
高影响因子
Cell Death & Disease
·
2021
·Vol. 12
·期 1
·1-16
·
IF 8.469
Yang Jin,Cao Lu-Lu,Wang Xi-Peng,Guo Wei,Guo Ruo-Bing,Sun Yu-Qin,Xue Teng-Fei,Cai Zhen-Yu,Ji Juan,Cheng Hong,Sun Xiu-Lan
Extracellular vesicles (EVs), as a novel intercellular communication carrier transferring cargo microRNAs (miRNAs), could play important roles in the brain remodeling process after ischemic stroke. However, the detailed mechanisms involved in EVs derived miRNAs-mediated cellular interactions in the brain remain unclear. Several studies indicated that microRNA-98 (miR-98) might participate in the pathogenesis of ischemic stroke. Here, we showed that expression of miR-98 in penumbra field kept up on the first day but dropped sharply on the 3rd day after ischemic stroke in rats, indicating that miR-98 could function as an endogenous protective factor post-ischemia. Overexpression of miR-98 targeted inhibiting platelet activating factor receptor-mediated microglial phagocytosis to attenuate neuronal death. Furthermore, we showed that neurons transferred miR-98 to microglia via EVs secretion after ischemic stroke, to prevent the stress-but-viable neurons from microglial phagocytosis. Therefore, we reveal that EVs derived miR-98 act as an intercellular signal mediating neurons and microglia communication during the brain remodeling after ischemic stroke. The present work provides a novel insight into the roles of EVs in the stroke pathogenesis and a new EVs-miRNAs-based therapeutic strategy for stroke.
研究领域:
神经科学
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分子生物学
·
细胞生物学
·
中风研究
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2021
·Vol. 476
·期 5
·2061-2073
·
IF 3.396
Wang Gang,Wang Hefeng,Zhang Lijuan,Guo Feng,Wu Xiangyu,Liu Yang
Studies have reported that miR-195-5p plays a role in the Hirschsprung disease (HSCR). Our previous work found GDNF family receptor alpha 4 (GFRA4) is also associated with HSCR. In this study, we focused on whether miR-195-5p induces the absence of enteric neurons and enteric neural crest in HSCR by regulating GFRA4. The expression levels of GFRA4 and miR-195-5p in colon tissues were evaluated by real-time PCR (RT-PCR) assay. We overexpressed GFRA4 or miR-195-5p in SH-SY5Y cells, the cell proliferation, cell cycle, apoptosis and invasion were subsequently investigated by CCK-8 assay, EdU staining, Flow cytometry analysis and Transwell assay, respectively. We also established the xenograft model to detect the effect of miR-195-5p on tumor growth and GFRA4 and p-RET expressions. GFRA4 expression was significantly downregulated in the HSCR colon tissues when compared with that in the control tissues. Overexpression of GFRA4 significantly promoted proliferation, invasion and cell cycle arrest, and inhibited apoptosis of SH-SY5Y cells. We also proved that GFRA4 is a direct target of miR-195-5p, and miR-195-5p inhibited proliferation, invasion, cell cycle arrest and differentiation, and accelerated apoptosis in SH-SY5Y cells which can be reversed by GFRA4 overexpression. Furthermore, we demonstrated that miR-195-5p suppressed tumor growth, and observably decreased GFRA4 and p-RET expressions. Our findings suggest that miR-195-5p plays an important role in the pathogenesis of HSCR. MiR-195-5p inhibited proliferation, invasion and cell cycle arrest, and accelerated apoptosis of nerve cells by targeting GFRA4.
研究领域:
分子生物学
·
神经科学
·
医学遗传学
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DOI
PubMed
高影响因子
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