Molecular Therapy-Nucleic Acids
·
2023
·
IF 8.8
Xinyi Gu,Shen Wang,Dongdong Li,Bo Jin,Zhidan Qi,Jin Deng,Chen Huang,Xiaofeng Yin
Peripheral nerve injury can lead to progressive muscle atrophy and poor motor function recovery, which is a difficult point of treatment, and the mechanism needs to be further explored. In previous studies we found that miR-142a-3p was significantly upregulated and persistently high expressed in denervated mouse skeletal muscle. Here, we show that overexpression of miR-142a-3p inhibited the growth and differentiation of C2C12 myoblast, while knockdown of miR-142a-3p had a promoting effect. In vitro, knockdown of miR-142a-3p in denervated mouse skeletal muscle effectively increased proliferating muscle satellite cells and ameliorated muscle atrophy. Mechanistically, the myoregulator Mef2a was proved to be an important downstream target of miR-142a-3p, and miR-142a-3p regulates skeletal muscle differentiation and regeneration by inhibiting the expression of Mef2a. The co-knockdown of Mef2a and miR-142a-3p effectively alleviated or offset the biological effects of miR-142a-3p knockdown. In conclusion, our data revealed that miR-142a-3p regulates neurogenic skeletal muscle atrophy by targeting Mef2a.
研究领域:
神经科学
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分子生物学
·
肌肉骨骼疾病
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DOI
PubMed
高影响因子
Molecular Therapy-Nucleic Acids
·
2023
·
IF 8.8
Chen Jun Guo,Xiu Li Cao,Yu Fei Zhang,Kang Yi Yue,Jing Han,Hong Yan,Hua Han,Min Hua Zheng
Inherited and age-related retinal degenerations are the commonest causes of blindness without effective treatments. Retinal progenitor cells (RPCs), which have the multipotency to differentiate into various retinal cell types, are regarded as a promising source of cell transplantation therapy for retinal degenerative diseases. However, the self-limited expansion of RPCs causes difficulty in cell source supply and restrict its clinical treatment. In this work, we found that inhibition of microRNA-449a (miR-449a) in RPCs can promote proliferation and inhibit apoptosis of RPCs, partially through upregulating Notch signaling. Further optimization of transduction miR-449a inhibitor into RPCs by endothelial cell-derived exosomes can promote the survival of RPCs transplanted in vivo and reduce cell apoptosis in retinal degeneration mouse models. In summary, these studies have shown that exosome-miR-449a inhibitor can effectively promote the expansion of RPCs in vitro and enhance transplanted RPCs survival in vivo , which might provide a novel intervention strategy for retinal degenerations in the future.
研究领域:
医学
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分子生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
RNA Biology
·
2019
·
IF 5.477
Kang He,Huamei Xiao,Yang Sun,Gongming Situ,Yu Xi,Fei Li
The precise increase and decrease of hormone ecdysone are critical for accurate development in insects. Most previous works focus on transcriptional activation of ecdysone production; however, little is known about the mechanism of switching off ecdysone biosynthesis after ecdysis. Here, we showed that the precursor microRNA-14 (pre-miR-14) encodes two mature miRNAs in silkworm; both of these two mature miRNAs regulate various genes in the ecdysone-signalling pathway. Bmo-miR-14-5p targets on nine genes whereas Bmo-miR-14-3p targets on two genes in the same pathway. These two mature miRNAs increased immediately after the ecdysis, efficiently suppressing the 20-hydroxyecdysone (20E) biosynthesis, the upstream regulation, and the downstream response genes. Knocking down either of two mature miRNAs or both of them delays moult development, impairing development synchrony in antagomir-treated groups. In addition, overexpressing Bmo-miR-14-5p but not Bmo-miR-14-3p significantly affected the 20E titer and increased the moulting time variation, suggesting that Bmo-miR-14-5p, though it is less abundant, has more potent effects in development regulation than Bmo-miR-14-3p. In summary, we present evidence that a pre-miRNA encodes two mature miRNAs targeting on the same pathway, which significantly improves miRNA regulation efficiencies to programmatically switch off ecdysone biosynthesis.
研究领域:
昆虫学
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分子生物学
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发育生物学
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DOI
PubMed
高影响因子
Nanoscale
·
2015
·Vol. 7
·期 19
·9055-9061
·
IF 7.394
Wenjiao Zhou,Wenbin Liang,Xin Li,Yaqin Chai,Ruo Yuan,Yun Xiang
The construction of DNA nanostructures with various sizes and shapes has significantly advanced during the past three decades, yet the application of these DNA nanostructures for solving real problems is still in the early stage. On the basis of microRNA-triggered, catalytic self-assembly formation of the functional “DNAzyme ferris wheel” nanostructures, we show here a new signal amplification platform for highly sensitive, label-free and non-enzyme colorimetric detection of a small number of human prostate cancer cells. The microRNA (miR-141), which is catalytically recycled and reused, triggers isothermal self-assembly of a pre-designed, G-quadruplex sequence containing hairpin DNAs into “DNAzyme ferris wheel”-like nanostructures (in association with hemin) with horseradish peroxidase mimicking activity. These DNAzyme nanostructures catalyze an intensified color transition of the probe solution for highly sensitive detection of miR-141 down to 0.5 pM with the naked eye, and the monitoring of as low as 283 human prostate cancer cells can also, theoretically, be achieved in a colorimetric approach. The work demonstrated here thus offers new opportunities for the construction of functional DNA nanostructures and for the application of these DNA nanostructures as an effective signal amplification means in the sensitive detection of nucleic acid biomarkers.
研究领域:
生物化学
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分子诊断
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纳米技术
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癌症研究
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DOI
PubMed
高影响因子
Genes & Genomics
·
2022
·Vol. 44
·期 8
·1017-1029
·
IF 2.164
Hou Fangxing,Li Xing,Wang Yanfeng,Xiao Xiangzuo
Background Liver regeneration is a highly orchestrated process concerning the modulation of various microRNAs (miRs). miR-183 was recently found to be involved in the process of liver regeneration, that miR-183 was remarkably up-regulated at 2–6 h after partial hepatectomy. Objective This study was aimed to explore the mechanism of miR-183 in on liver regeneration. Methods After partial hepatectomy (PH) or transfection, we measured the changes of miR-183 and programmed cell death protein 6 (PDCD6) levels in rats and the hepatocytes. The histopathology was observed with hematoxylin–eosin staining. The miR-183 mimic and inhibitor plasmids were intravenously injected into rats, and the liver weight/body weight ratio was calculated. The prediction of TargetScan and the validation of luciferase activity assay were employed to confirm the targeting relationship between miR-183 and PDCD6. The viability, apoptosis and cell cycle of transfected rat hepatocyte BRL-3A were determined via MTT and flow cytometry assays. Results MiR-183 expression showed a contrary tendency with that of PDCD6 during liver regeneration. Enhanced miR-183 in rats could notably increase liver/body weight ratio, while its inhibition did conversely. Overexpressed PDCD6, a target of miR-183, repressed the viability and cell cycle in hepatocytes, whereas its silence led to contrary results. Overexpressed miR-183 in BRL-3A cells enhanced cell viability and promoted the cell cycle yet suppressed apoptosis, whereas its inhibition showed contrary results, which were offset by PDCD6. Conclusions Collectively, miR-183 promoted liver regeneration via targeting PDCD6.
研究领域:
分子生物学
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肝病学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Cardiovascular Medicine
·
2022
·
IF 5.846
Hongge Fa,Dandan Xiao,Wenguang Chang,Lin Ding,Lanting Yang,Yu Wang,Mengyu Wang,Jianxun Wang
Objective Many studies have reported that microRNAs (miRs) are involved in the regulation of doxorubicin (DOX)-induced cardiotoxicity. MiR-194-5p has been reported significantly upregulated in patients with myocardial infarction; however, its role in myocardial diseases is still unclear. Various stimuluses can trigger the endoplasmic reticulum (ER) stress and it may activate the apoptosis signals eventually. This study aims to explore the regulatory role of miR-194-5p in DOX-induced ER stress and cardiomyocyte apoptosis. Methods H9c2 was treated with 2 μM DOX to induce apoptosis, which is to stimulate the DOX-induced cardiotoxicity model. The expression of miR-194-5p was detected by quantitative real-time PCR (qRT-PCR); the interaction between miR-194-5p and P21-activated kinase 2 (PAK2) was tested by dual luciferase reporter assay; terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and caspase-3/7 activity were used to assess apoptosis; trypan blue staining was applied to measure cell death; Western blotting was performed to detect protein expressions; and ER-related factors splicing X-box binding protein 1 (XBP1s) was detected by polyacrylamide gel electrophoresis and immunofluorescence to verify the activation of ER stress. Results MiR-194-5p was upregulated in cardiomyocytes and mouse heart tissue with DOX treatment, while the protein level of PAK2 was downregulated. PAK2 was predicted as the target of miR-194-5p; hence, dual luciferase reporter assay indicated that miR-194-5p directly interacted with PAK2 and inhibited its expression. TUNEL assay, caspase-3/7 activity test, and trypan blue stain results showed that either inhibition of miR-194-5p or overexpression of PAK2 reduced DOX-induced cardiomyocyte apoptosis. Silencing of miR-194-5p also improved DOX-induced cardiac dysfunction. In addition, DOX could induce ER stress in H9c2, which led to XBP1 and caspase-12 activation. The expression level of XBP1s with DOX treatment increased first then decreased. Overexpression of XBP1s suppressed DOX-induced caspase-3/7 activity elevation as well as the expression of cleaved caspase-12, which protected cardiomyocyte from apoptosis. Additionally, the activation of XBP1s was regulated by miR-194-5p and PAK2. Conclusion Our findings revealed that silencing miR-194-5p could alleviate DOX-induced cardiotoxicity via PAK2 and XBP1s in vitro and in vivo . Thus, the novel miR-194-5p/PAK2/XBP1s axis might be the potential prevention/treatment targets for cancer patients receiving DOX treatment.
研究领域:
心脏病学
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分子生物学
·
药理学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Tianjiao Meng,Huixian Jia,Siying An,Huan Wang,Xinjian Yang,Yufan Zhang
Herein, a Pd nanoparticles-DNA layered nanoreticulation (Pd NPs-DNA LNR) sensor was assembled to a graphene oxide (GO)-modified electrode by catalytic hairpin assembly (CHA) and a self-assembly process. In this process, GO was modified on the electrode surface to provide -COOH sites for DNA bonding. Moreover, with the CHA circular amplification strategy, many single DNA1 were exposed to be able to be bound with Pd-DNA2 for the formation of the Pd NPs-DNA LNR, which enabled the ultrasensitive detection of microRNA-21 (miR-21) with a low limit of detection 63.1 aM. This strategy combines the amplification technology of CHA and Pd NPs-DNA LNR with Pd NPs. Such a layered nanoreticulation material can support abundant Pd NPs to avoid aggregation and obtain enhanced electrochemical signals. Significantly, this method can be successfully applied in tumor cell lysates and provides a neoteric channel for early disease diagnosis.
研究领域:
生物传感器技术
·
分子诊断学
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DOI
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Zhenmao Chen,Yijing Ai,Weiqiang Yang,Li Niu,Qingxiang Wang,Feng Gao
The unique discriminating ability of hydroxyapatite (HAP) to single- and double-stranded nucleic acid implies its potential as a biosensing material for nucleic acid analysis. Herein, a novel immobilization- and label-free electrochemical strategy has been developed for miRNA let-7a detection based on the specific adsorption of magnetic Fe3O4@hydroxyapatite (Fe3O4@HAP) to a duplex structure. Typically, the highly efficient homogeneous reaction between probe DNA (pDNA) and target miRNA let-7a produces the nucleic acid duplex, which is specifically adsorbed on the surface of Fe3O4@HAP. Thereafter, the electroactive intercalator Nile blue (NB) is introduced as the label-free signal molecule and inserts between the stacked base pairs of the pDNA–miRNA duplex. Thus, the Fe3O4@HAP bearing pDNA–miRNA and numerous intercalated NBs are adsorbed by the magnetic glassy carbon electrode, giving rise to an intense sensing signal without the need of nuclease-assisted cyclic amplification. With this advantage, the sensing system shows a wide linear range from 1.0 fM to 100 nM and a low detection limit of 0.051 fM for miRNA let-7a analysis. What is more, the synergy of the base-pairing-driven hybridization, the specific intercalation of NB to the duplex structure, and the selective adsorption of Fe3O4@HAP contribute to a high sensing specificity of the biosensing strategy. The sensing method provides a state-of-the-art strategy for the sensitive and facile bioanalysis and clinical diagnosis of miRNA.
研究领域:
生物传感
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分子诊断
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材料科学
·
分析化学
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产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Yuchen Song,Changqing Mao,Wenjiao Zhang,Dongmei Deng,Huinan Chen,Pei Sun,Meiyin Liu,Chang Feng,Liqiang Luo
The low abundance, heterogeneous expression, and temporal changes of miRNA in different cellular locations pose significant challenges for both the detection sensitivity of miRNA liquid biopsy and intracellular imaging. In this work, we report an intelligently assembled biosensor based on catalytic hairpin assembly (CHA) and aggregation-induced emission (AIE), named as catalytic hairpin aggregation-induced emission (CHAIE), for the ultrasensitive detection and intracellular imaging of miRNA-155. To achieve such goal, tetraphenylethylene-N 3 (TPE-N 3 ) is used as AIE luminogen (AIEgen), while graphene oxide is introduced to quench the fluorescence. When the target miRNA is present, CHA reaction is triggered, causing the AIEgen to self-assemble with the hairpin DNA . This will restrict the intramolecular rotation of the AIEgen and produce a strong AIE fluorescence. Interestingly, CHAIE does not require any enzyme or expensive thermal cycling equipment, and therefore provides a rapid detection. Under optimal conditions, the proposed biosensor can determine miRNA in the concentration range from 2 pM to 200 nM within 30 min, with the detection limit of 0.42 pM. The proposed CHAIE biosensor in this work offers a low background signal and high sensitivity, making it applicable for highly precise spatiotemporal imaging of target miRNA in living cells.
研究领域:
分子生物学
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生物传感
·
医学影像
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xiaomei Mu,Shixiu Xiao,Shulin Zhao,Jianniao Tian
In this work, a fast signal amplification system mediated by self-replicating catalytic hairpin self-assembly (SCHA) was established for microRNA-155 using near-infrared DNA-Ag Nanoclusters (DNA-AgNCs) as fluorescence signal output. Among them, two fission target-like DNA sequences are merged into two hairpin DNA H1 and H2, and the AgNCs template sequence is designed at the sticky end of H1 and H2. The target can be recycled in the system to form a double-stranded DNA structure (H1–H2), which will detach the H1/H2-AgNCs from the surface of the polypyrrole nanoparticles (PPy NPs) and cause the near-infrared fluorescence signal of DNA-AgNCs to be restored. At this point, the two-split target-like DNA sequences will be reassembled to initiator DNA. The acquired replicas can also be recycled as a brand-new activation unit to initiate the SCHA response, resulting in rapid replication of the target/triggered DNA, accompanied by the generation of higher fluorescence signals. This autocatalytic signal amplification approach has been successfully applicable to fast signal amplification, enzyme-free and label-free for microRNA-155 assay in biological samples, and the detection limit (LOD) is 240 fM (S/N = 3). At the same time, this SCHA system can realize intracellular microRNA fluorescence imaging, which presents a promising approach to developing advanced molecular diagnostic tools.
研究领域:
生物化学
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分子生物学
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医学诊断
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Wei Wei,Yuanyuan Yao,Hongyuan Bi,Wenxin Xu,Yan Gao
Our previous findings revealed that hsa_circ_0068,888 was markedly down-regulated in the plasma of patients with sepsis-associated acute kidney injury (AKI). However, its molecular mechanism in AKI remains unclear. Herein, we explored the role of hsa_circ_0068,888 in AKI. Human renal proximal tubular cell line HK-2 was stimulated with lipopolysaccharide (LPS) to mimic AKI in vitro . Decreased hsa_circ_0068,888 expression was observed in AKI cell model. The overexpression of hsa_circ_0068,888 significantly increased the viability of LPS-stimulated HK-2 cells, whereas hsa_circ_0068,888 downregulation showed the opposite effect. Furthermore, LPS triggered inflammatory response and oxidative stress , which was inhibited by hsa_circ_0068,888 overexpression and enhanced by hsa_circ_0068,888 down-regulation. Hsa_circ_0068,888 overexpression suppressed the activation of nuclear factor-κB (NF-κB) pathway triggered by LPS as evidenced by decreased p-p65 protein level and nuclear translocation of p65 in hsa_circ_0068,888 overexpressed cells. Additionally, we proved that hsa_circ_0068,888 targeted microRNA-21–5p (miR-21–5p). The expression of miR-21–5p was markedly increased and was negatively regulated by hsa_circ_0068,888 in LPS-stimulated HK-2 cells. Furthermore, we demonstrated that miR-21–5p overexpression reversed the effects on cell viability , inflammatory response, oxidative stress, and NF-κB pathway induced by hsa_circ_0068,888 overexpression in LPS-stimulated HK-2 cells. Overall, these results implied that hsa_circ_0068,888 shows a protective effect on AKI by sponging miR-21–5p. Hence, up-regulation of hsa_circ_0068,888 might be a potential strategy in treatment for AKI.
研究领域:
分子生物学
·
细胞生物学
·
肾脏病学
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产品关联
DOI
PubMed
高影响因子
ELECTROCHIMICA ACTA
·
2022
·
IF 7.336
Qianqing Wu,Zhenhui Li,Qianwei Liang,Rongkai Ye,Shuzhou Guo,Xiaobing Zeng,Jianqiang Hu,Aiqing Li
MicroRNAs (miRNAs) are considered as potential biomarkers for early diagnosis and prognostic assessment of diabetic nephropathy. In this work, an electrochemical biosensor for ultrasensitive detection of miRNA-377 was constructed based on MXene-Au nanocomposites and G-quadruplex nano-amplification strategy. As a promising nanocarrier, taking advantage of leveraging synergistic effects between Au nanoparticles (AuNPs) and MXene nanosheet, MXene-Au nanocomposites exhibited excellent electronic conductivity and provided massive active sites for DNA capture probe immobilization by Au-S bonds. AuNPs modified with Guanine-rich sequence DNA detection probes were designed as signal amplification nano-labels. Specifically, by inducing the transition of Guanine-rich detection probes to G-quadruplex, the strong affinity interaction between methylene blue and G-quadruplex could not only reflect trace concentration information of miRNA-377, but also lead to the further enhancement of electrochemical signal (2.7-fold). As a result, this newly designed biosensor exhibited superior sensing performance with a wide linear range from 10 aM to 100 pM and the limit of detection was as low as 1.35 aM. Compared with biosensors based on other nanocomposites and reported miRNA-377 biosensors, the proposed sensing platform did not require any thermal cycling or reverse transcription process, meeting the miRNA sensing requirements of convenient, sensitive, specific and stable. Furthermore, the as-constructed biosensor also displayed good selectivity, which was applied to accurate detection of miRNA-377 in human serum samples with satisfactory sensitivity, suggesting the biosensor system has promising applications in biological researches and early clinical diagnosis for diabetic nephropathy.
研究领域:
生物医学工程
·
分析化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）