JOURNAL OF CELLULAR PHYSIOLOGY
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2020
·
IF 5.546
Tao Bai,Ruopeng Liang,Rongtao Zhu,Weijie Wang,Lin Zhou,Yuling Sun
Primary liver cancer is the second most frequent cause of cancer-related deaths. Ferroptosis, a recognized form of regulated cell death, recently gains attention. MicroRNA-214-3p (miR-214) plays a regulatory role in hepatocarcinogenesis. However, the role of miR-214 in cellular ferroptosis is unclear. This study aimed at elucidating whether miR-214 could regulate ferroptosis of liver cancer. In vitro, HepG2 and Hep3B cancer cells were treated with erastin, a ferroptosis inducer, and then erastin was demonstrated to suppress the cell viability. Moreover, pre-miR-214 overexpression caused that HepG2 and Hep3B cells were more susceptible to erastin, whereas anti-miR-214 sponge showed the opposite effect. Additionally, pre-miR-214 overexpression increased the malondialdehyde and reactive oxygen species levels, upregulated Fe 2+ concentration, and decreased glutathione levels in cancer cells exposed to erastin. Further, erastin enhanced the activation of transcription factor 4 (ATF4) in HepG2 and Hep3B cells, and pre-miR-214 overexpression inhibited ATF4 expression. The luciferase reporter data validated ATF4 as a direct target of miR-214. Cancer cells transfected with ATF4 overexpression plasmid rendered lower susceptible to miR-214-induced ferroptotic death. In vivo, erastin significantly reduced the size and weight of xenografted tumors, and miR-214 elevated the ferroptosis-promoting effects of erastin and decreased ATF4 expression. In summary, our study demonstrates that the ferroptosis-promoting effects of miR-214 in hepatoma cells are attributed at least to its inhibitory effects on ATF4, which may provide a new target for therapy of hepatoma regarding ferroptosis.
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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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Dan Su,Zhong Chen,Xiaobin An,Junkai Yang,Jinan Yang,Xuqiao Wang,Yang Qu,Chen Gong,Yani Chai,Xiaoying Liu,Wei Cheng,Dongyang Wang,Yan Wu,Jing Ma,Xinyue Zhao,Qin Wang,Yun Xu,Haisheng Peng,Jing Ai
The complex etiologies and mechanisms of Alzheimer's disease (AD) underscore the importance for devising multitarget drugs to achieve effective therapy. MicroRNAs (miRNAs) are capable of concurrently regulating the expression of multiple proteins by selectively targeting disease- associated genes in a sequence-specific fashion. Nonetheless, as RNA-based drugs, their stability in the circulation and capacity of traversing the blood–brain barrier (BBB) is largely compromised, thereby limiting their potential clinical applications. In this study, we formulated the nanoliposomes encapsulating polyethyleneimine (PEI)/ miR-195 complex (DPMT@PEI/ miR-195 ) that was engineered through dual modifications to contain P -aminophenyl-alpha-d-mannopyranoside (MAN) and cationic cell-penetrating peptide (TAT). DPMT@PEI/ miR-195 exhibited the enhanced BBB- and cell membrane penetrating capability. As expected, we observed that DPMT@PEI/ miR-195 administered through intravenous tail injection of produced greater effectiveness than donepezil and the same range of effect as aducanumab in alleviating the cognitive decline in 7-month-old APP/PS1 mice. Moreover, the combination treatment with DPMT@PEI/ miR-195 and donepezil effectively ameliorated the deterioration of cognition in 16-month-old APP/PS1 mice, with enhanced effects than either DPMT@PEI/ miR-195 or donepezil alone. Furthermore, DPMT@PEI/ miR-195 effectively attenuated the positive signals of Aβ, AT8, and CD68 in APP/PS1 mice without notable side effects. Our findings indicate DPMT@PEI/ miR-195 as a promising potentially new agent or approach for the prophylaxis and treatment of early and advanced stages of Alzheimer's disease.
研究领域:
神经科学
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药理学
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分子生物学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Weipan Peng,Qian Zhao,Jiafang Piao,Miao Zhao,Yiwen Huang,Bo Zhang,Weichen Gao,Dianming Zhou,Guiming Shu,Xiaoqun Gong,Jin Chang
The detection and analysis of microRNA (miRNA) can provide critical information for biomedical research and clinical diagnosis. In this paper, we constructed a simple method to achieve ultra-sensitive and rapid detection of miRNA based on the double-specific nuclease (DSN) assisting target recovery and horseradish peroxidase (HRP) cascading signal amplification. In the existence of target microRNA-21 (miR-21), the DSN enzyme specifically cut the single-stranded DNA (ssDNA) hybridized with the target miRNA but still kept the target miRNA intact, so there were more free HRP released from the polystyrene microparticles-ssDNA-HRP conjugates (PS-ssDNA-HRP) because of the target recycle and signal amplification. The free HRP in the supernatant were collected to react with the substrate 3,3',5,5'-tetramethylbenzidine (TMB). The color and absorbance changes of HRP-TMB system further resulted in qualitative screening by naked eyes and quantitative detection by the microplate reader with the detection limit as low as 3.1 fM. This assay protocol not only showed high sensitivity and selectivity, but also well distinguished the difference between the miRNA family members, as well as the simple operation, fast detection, naked eye qualitative and microplate reader quantification. It has great application value in the biomedical research and clinical diagnosis.
研究领域:
分子生物学
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临床诊断
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生物化学
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产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
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IF 8.4
Qingteng Lai,Yanke Zhang,Wei Chen,Zhengchun Liu
In this study, an ultrasensitive electrochemical-detection system based on a target “turn-on” signal-enhancement pseudocapacitor was established for microRNA-141 (miRNA-141) detection. A three-dimensional porous film was constructed on the electrode surface in situ by chitosan, catechol and nanomaterials (gold nanoparticles and nitrogen-doped carbon nanotubes). When miRNA-141 hybridized with the probe on the electrode, ferrocene (Fc) was specifically introduced into the electrode surface, and then a pseudocapacitor containing Fc, ruthenium ion (Ru 3+ ), catechol, and electrode formed (“turn on”). Fc and Ru 3+ consumed in the electrode reaction can quickly recover to the original valence state on the surface of catechol/quinone and again participated in the electrode reaction. A "one to many" relationship existed between the target and the signal molecule Fc, which contributed to the improvement of the sensor sensitivity. The signal strength and stability of Fc improved and thus improved the sensitivity and stability of miRNA-141 detection. The concentration information of miRNA-141 was collected from the change in Fc signal strength. The linear detection range was 0.5 fM to 800 pM, and the detection limit can be calculated as 43.73 aM. This system overcame the problems of low reliability and weak signal of the traditional electroactive-ion labeling method, which relied on the change in electrostatic attraction/repulsion before and after probe–target hybridization.
研究领域:
生物化学
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纳米技术
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电化学
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生物传感器
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癌症诊断
✓ 已验证
产品关联
DOI
高影响因子
Cell Communication and Signaling
·
2020
·Vol. 18
·期 1
·1-16
·
IF 4.344
Yan Mei-Ling,Zhang Shuai,Zhao Hong-Mei,Xia Sheng-Nan,Jin Zhuo,Xu Yi,Yang Lin,Qu Yang,Huang Si-Yu,Duan Ming-Jing,Mao Meng,An Xiao-Bin,Mishra Chandan,Zhang Xin-Yu,Sun Li-Hua,Ai Jing
Background Chronic brain hypoperfusion (CBH) is closely related to Alzheimer’s disease (AD) and vascular dementia (VaD). Meanwhile, synaptic pathology plays a prominent role in the initial stage of AD and VaD. However, whether and how CBH impairs presynaptic plasticity is currently unclear.Methods In the present study, we performed a battery of techniques, including primary neuronal culture, patch clamp, stereotaxic injection of the lentiviral vectors, morris water maze (MWM), dual luciferase reporter assay, FM1–43 fluorescence dye evaluation, qRT-PCR and western blot, to investigate the regulatory effect of miR-153 on hippocampal synaptic vesicle release both in vivo and in vitro. The CBH rat model was generated by bilateral common carotid artery ligation (2VO).Results Compared to sham rats, 2VO rats presented decreased field excitatory postsynaptic potential (fEPSP) amplitude and increased paired-pulse ratios (PPRs) in the CA3-CA1 pathway, as well as significantly decreased expression of multiple vesicle fusion-related proteins, including SNAP-25, VAMP-2, syntaxin-1A and synaptotagmin-1, in the hippocampi. The levels of microRNA-153 (miR-153) were upregulated in the hippocampi of rats following 2VO surgery, and in the plasma of dementia patients. The expression of the vesicle fusion-related proteins affected by 2VO was inhibited by miR-153, elevated by miR-153 inhibition, and unchanged by binding-site mutation or miR masks. FM1–43 fluorescence images showed that miR-153 blunted vesicle exocytosis, but this effect was prevented by either 2′-O-methyl antisense oligoribonucleotides to miR-153 (AMO-153) and miR-masking of the miR-153 binding site in the 3′ untranslated region (3’UTR) of the Snap25, Vamp2, Stx1a and Syt1 genes. Overexpression of miR-153 by lentiviral vector-mediated miR-153 mimics (lenti-pre-miR-153) decreased the fEPSP amplitude and elevated the PPR in the rat hippocampus, whereas overexpression of the antisense molecule (lenti-AMO-153) reversed these changes triggered by 2VO. Furthermore, lenti-AMO-153 attenuated the cognitive decline of 2VO rats.Conclusion sOverexpression of miR-153 controls CBH-induced presynaptic vesicle release impairment by posttranscriptionally regulating the expression of four vesicle release-related proteins by targeting the 3’UTRs of the Stx1a, Snap25, Vamp2 and Syt1 genes. These findings identify a novel mechanism of presynaptic plasticity impairment during CBH, which may be a new drug target for prevention or treatment of AD and VaD.
Video Abstract
Graphical abstract
研究领域:
神经科学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2023
·
IF 4.5
Dongsheng Zhu,Zhitao Zhu,Han Qi
Objective Long non-coding RNA plays an important role in osteogenic differentiation. Nuclear enriched abundant transcript 1 (NEAT1) has been revealed to promote osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs), but the underlying regulatory mechanism remains unknown in acute suppurative osteomyelitis of children.Methods Osteogenic medium (OM) was used to induce osteogenic differentiation. Quantitative real-time PCR and Western blotting were used to evaluate gene expression. The effects of NEAT1, microRNA 339–5p (miR-339-5p), and salmonella pathogenicity island 1 (SPI1) on osteogenic differentiation were assessed in vitro using alizarin red S staining assays and alkaline phosphatase activity. Interactions between NEAT1, miR-339-5p, and SPI1 were identified using immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation.Results During osteogenic differentiation, expression of NEAT1 was up-regulated in hBMSCs, and miR-339-5p level was down during osteogenic differentiation. Knockdown of NEAT1 reduced the osteogenic differentiation of hBMSCs, and down-regulation of miR-339-5p may counteract the effect of NEAT1 silencing. SPI1 was a target of miR-339-5p by luciferase reporter assay and was also a transcription factor of NEAT1 by chromatin immunoprecipitation. A positive NEAT1-miR-339-5p-SPI1 feedback loop was found to be present during osteogenic differentiation in hBMSCs.Conclusion It was the first study to reveal that the NEAT1-miR-339-5p-SPI1 feedback loop can promote osteogenic differentiation in hBMSCs and shed a new light on the role of NEAT1 during osteogenic differentiation.
研究领域:
分子生物学
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细胞生物学
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医学遗传学
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儿科
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DOI
PubMed
高影响因子
Scientific Reports
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2015
·Vol. 5
·期 1
·1-10
·
IF 5.578
Zhang Yong,Qin Wei,Zhang Longyin,Wu Xianxian,Du Ning,Hu Yingying,Li Xiaoguang,Shen Nannan,Xiao Dan,Zhang Haiying,Li Zhange,Zhang Yue,Yang Huan,Gao Feng,Du Zhimin,Xu Chaoqian,Yang Baofeng
Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke. Endothelial apoptosis plays a vital role in the initiation and progression of atherosclerotic lesions. Although a subset of microRNAs (miRs) have been identified as critical regulators of atherosclerosis, studies on their participation in endothelial apoptosis in atherosclerosis have been limited. In our study, we found that miR-26a expression was substantially reduced in the aortic intima of ApoE −/− mice fed with a high-fat diet (HFD). Treatment of human aortic endothelial cells (HAECs) with oxidized low-density lipoprotein (ox-LDL) suppressed miR-26a expression. Forced expression of miR-26a inhibited endothelial apoptosis as evidenced by MTT assay and TUNEL staining results. Further analysis identified TRPC6 as a target of miR-26a and TRPC6 overexpression abolished the anti-apoptotic effect of miR-26a. Moreover, the cytosolic calcium and the mitochondrial apoptotic pathway were found to mediate the beneficial effects of miR-26a on endothelial apoptosis. Taken together, our study reveals a novel role of miR-26a in endothelial apoptosis and indicates a therapeutic potential of miR-26a for atherosclerosis associated with apoptotic cell death.
研究领域:
心血管疾病
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
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2021
·
IF 5.097
Xing-Yuan Du,Shao-Hua Wu,Xiao-Bin Huang,Jian-Jun Sun
Surface-enhanced Raman scattering (SERS)-based biosensing has strong potential owing to its high sensitivity and good selectivity. In this study, a SERS biosensing platform for microRNA-21 detection was proposed by combining heating-enhanced duplex-specific nuclease (DSN)-assisted target recycling amplification and silver nanocube (AgNC)-based SERS enhancement. The activity of DSN was greatly enhanced by increasing the surface temperature of a heated Au electrode (HAuE) during the DSN-assisted target recycling process, resulting in dramatic miRNA-21 amplification detection. 4-Mercaptobenzoic acid (4-MBA) acting as a Raman reporter was immobilized onto the surface of AgNC to form a AgNC/4-MBA SERS tag with AgNC providing significantly larger electric field enhancement and thus excellent SERS applications compared with conventional silver or gold nanospheres. This enhancement was attributed to the well-known “lighting rod” effect derived from the sharp geometrical feature of the edges and corners of AgNCs. These factors lead to the high sensitivity of the proposed SERS biosensor for the miRNA-21 measurement. A limit of detection of 2.88 fM (S/N = 3) was achieved at an electrode temperature of 55 °C, which was decreased by more than three magnitudes compared with that at 25 °C.
研究领域:
生物传感
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分子诊断
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纳米技术
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产品关联
DOI
高影响因子
JOURNAL OF BIOSCIENCES
·
2021
·Vol. 46
·期 1
·1-12
·
IF 1.826
Yang Mingzhu,Wang Li
Asthma has significant impacts on living quality particularly in children. Long noncoding RNA (lncRNA) MALAT1 plays a crucial role in neonatal respiratory diseases. Meanwhile, MALAT1 knockdown could induce viability and attenuate apoptosis of airway-related cells. However, the role of MALAT1 in neonatal asthma, asthma-related cell, and its possible mechanism is unclear. This study aims to investigate MALAT1 level in asthma and to identify the effects of MALAT1 on bronchial/tracheal smooth muscle cells (B/TSMCs). Newborn asthma modeling rat was constructed by introducing ovalbumin (OVA). MALAT1 levels in tissues or B/TSMCs were determined by RT-qPCR. Exogenous changes of MALAT1, RyR2 or miR-133a in B/TSMCs were fulfilled by cell transfection; cell apoptosis was measured by using Cell Death Detection ELISA kit and Hochest33342; IL-6, TNF-α and IL-1β level was detected by using corresponding ELISA kit; ryanodine receptor 2 (RyR2) mRNA and miR-133a level was determined by RT-qPCR; cleaved caspase-3 (c-caspase-3) and RyR2 expression was detected by Western blot; luciferase reporter assay was performed to confirm the target regulation of miR-133a on RyR2. We found that MALAT1 was significantly upregulated in tracheal tissues of newborn asthma modeling rats. In MALAT1-silenced or -overexpressed B/TSMCs, we found a synchronous change of cell apoptosis, inflammatory factor secretion (IL-6, TNF-α, and IL-1β) or RyR2 level, but a reverse change of miR-133a level with MALAT1. Besides, MALAT1 induced B/TSMCs apoptosis and inflammation increase could be partially reversed when RyR2 was silenced or when miR-133a was overexpressed. The luciferase reporter assay confirmed that RyR2 is a direct target gene of miR-133a in B/TSMCs. Finally, we conclude that MALAT1 knockdown could protect from B/TSMCs injury via regulating miR-133a/RyR2 axis.
研究领域:
呼吸医学
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分子生物学
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细胞生物学
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产品关联
DOI
高影响因子
EXPERIMENTAL DERMATOLOGY
·
2020
·Vol. 30
·期 7
·932-942
·
IF 3.368
Aimin Liu,Buxin Zhang,Wei Zhao,Yuanhui Tu,Qingxing Wang,Jing Li
Psoriasis is a chronic inflammatory disease characterized by abnormal hyperproliferation and differentiation. The object of this study is to explore the role of microRNA-215-5p in psoriasis-like inflammation. The expression of miR-215-5p was found to be down-regulated in pro-inflammatory factor-stimulated HaCaT cells and imiquimod (IMQ)-treated skin tissues. Overexpression of miR-215-5p suppressed the proliferation and cell cycle progression of HaCaT cells. Further, miR-215-5p agomir alleviated the disease severity, pathological features and Ki67 positive cells in IMQ-treated mice. Luciferase assay confirmed that miR-215-5p could bind to the 3′UTR of DYRK1A. The in vitro and in vivo results showed that miR-215-5p negatively regulates DYRK1A, which further inhibited EGFR and its downstream signalling pathways, AKT and ERK. Collectively, our results provide evidence that overexpression of miR-215-5p inhibits the proliferation of HaCaT cells and alleviates psoriasis-like inflammation partly by DYRK1A mediated inhibition of the EGFR signalling pathway. miR-215-5p may serve as a novel small molecule for therapeutic intervention in psoriasis.
研究领域:
分子生物学
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皮肤科
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炎症性疾病
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微小RNA研究
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2018
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IF 5.123
Jiafang Piao,Qian Zhao,Dianming Zhou,Weipan Peng,Weichen Gao,Minghui Chen,Guiming Shu,Xiaoqun Gong,Jin Chang
MicroRNAs (miRNAs) were reported to be potential tumor markers for early diagnosis of cancer. Due to its short sequence, low expression level and high susceptibility to degradation, the stable and sensitive detection method of miRNAs is arduous to establish. In this work, we designed a metal chelator (ethylenediamine tetraacetic acid disodium salt, EDTA•2Na) labeled oligonucleotides as the plasmonic signal supraregulator probe to control the generation of gold nanoparticles (AuNPs). Based on another complementary oligonucleotides of target miRNA labeling SiO 2 microparticles (SiO 2 MPs) as the detecting platform, EDTA•2Na labeled oligonucleotide probes were immobilized on the SiO 2 platform through the sandwich structure in the presence of target miRNA. The sandwich chelating device could further chelate Au 3+ to regulate the generation of AuNPs, resulting in colorimetric signal to qualitatively and quantitatively detect the concentration of microRNA-21 (miR-21). The results indicate that the proposed metal chelator -labeled signal amplification method has outstanding sensitivity (LOD = 8.9 fM) and excellent stability, which will be benefit for the early accurate diagnosis of miRNAs.
研究领域:
生物化学
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纳米技术
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癌症研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
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2021
·
IF 3.269
Bo Li,Xianyi Liu,Guogang Wu,Jiawen Liu,Shouliang Cai,Fuxin Wang,Chunyu Yang,Jisheng Liu
Colorectal cancer (CRC) is a global public health issue with increasing prevalence. MicroRNA-934 (miR-934) is a kind of non-coding RNA involved in the regulation of diverse cancers. Though previous researches have revealed part of association between miR-934 and CRC, the role of miR-934 in CRC pathogenesis has not been completely explored yet. In this study, we aim to investigate the effect of miR-934 on cell proliferation, migration, invasion and angiogenesis in CRC. Accordingly, miR-934 was found to be over-expressed in SW480 and HCT116 cells, two typical CRC cell lines. Meanwhile, miR-934 knockdown significantly inhibited cell proliferation and induced cell cycle arrest in SW480 and HCT116 cells. It was further validated that miR-934 knockdown displayed an inhibitory effect on cell migration and invasion in SW480 and HCT116 cells. Additionally, miR-934 deficiency markedly decreased VEGF expression in SW480 and HCT116 cells and suppressed capability of CRC cells to promote tube formation in vascular endothelial cells, which suggests the pro-angiogenesis role of miR-934 in vitro. Dual luciferase reporter assay further showed that miR-934 directly bound to B-cell translocation gene 2 (BTG2). BTG2 knockdown reversed the inhibitory effect of miR-934 silencing on cell proliferation, migration, invasion, and angiogenesis in SW480 and HCT116 cells. In summary, this study suggests that miR-934 facilitates CRC progression by targeting BTG2, and further highlights the role of miR-934 in pathogenesis of CRC.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）