Frontiers in Plant Science
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2020
·
IF 4.402
Wei Shuai-Jie,Chai Sen,Zhu Rui-Min,Duan Cun-Ying,Zhang Yan,Li Sha
Ovules are female reproductive organs of angiosperms, containing sporophytic integuments and gametophytic embryo sacs. After fertilization, embryo sacs develop into embryos and endosperm whereas integuments into seed coat. Ovule development is regulated by transcription factors (TF) whose expression is often controlled by microRNAs. Mutations of Arabidopsis DICER-LIKE 1 (DCL1), a microRNA processing protein, caused defective ovule development and reduced female fertility. However, it was not clear whether other microRNA processing proteins participate in this process and how defective ovule development influenced female fertility. We report that mutations of HUA ENHANCER1 (HEN1) and HYPONASTIC LEAVES 1 (HYL1) interfered with integument growth. The sporophytic defect caused abnormal embryo sac development and inability of mutant ovules to attract pollen tubes, leading to reduced female fertility. We show that the role of HEN1 in integument growth is cell-autonomous. Although AUXIN RESPONSE FACTOR 6 (ARF6) and ARF8 were ectopically expressed in mutant ovules, consistent with the reduction of microRNA167 in hen1, introducing arf6;arf8 did not suppress ovule defects of hen1, suggesting the involvement of more microRNAs in this process. Results presented indicate that the microRNA processing machinery is critical for ovule development and seed production through multiple microRNAs and their targets.
研究领域:
植物学
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遗传学
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分子生物学
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DOI
PubMed
高影响因子
Molecular Genetics & Genomic Medicine
·
2020
·Vol. 8
·期 5
·e1195
·
IF 1.995
Fei Cui,Zhe-xue Hao,Jin Li,Ya-lei Zhang,Xu-kai Li,Jian-xing He
Background This study is aimed to unravel the genetic factors associated with microRNA (miRNA) expression in regulating sex-determining region Y-box 2 ( SOX2 )-mediated cisplatin resistance in small-cell lung cancer (SCLC). Methods The relevance of SOX2 expression in SCLC was analyzed in a panel of SCLC cells by quantitative real-time PCR (qPCR) and western blot (WB). We selected DMS114 cell line, in which SOX2 was amplified via lentiviral vector-mediated transfection of the SOX2 genes and tested for the half-maximal inhibitory concentration (IC 50 ) by MTS assay. High-throughput sequencing and screening of differentially expressed miRNAs between SOX2 -overexpressing and normal control cells were performed. Finally, miRanda software was used to verify the miRNAs bound with SOX2 and qPCR was used to identify the expression of miRNAs which were binding with SOX2 . Results Cisplatin-resistant SOX2 -overexpressing DMS114 cell lines were successfully developed, showing a statistically significant increase in SOX2 expression by qPCR and WB. Our results showed a typically higher IC 50 value in SOX2 -overexpressing cells compared with the negative controls. The high-throughput sequencing analysis revealed that 68 miRNAs were upregulated and 24 miRNAs were downregulated in the SOX2 -overexpressing cells. The 24 downregulated miRNAs were further verified. Of them, a cancer-related miRNA, hsa-miR-340-5p, showed a higher binding affinity with SOX2 in network regulation mapping, which was also found to be markedly downregulated under qPCR analysis. Conclusion We demonstrated that downregulated expression of hsa-miR-340-5p may affect cisplatin resistance by mediating SOX2 expression in SCLC cells, which may provide a potential target for the therapy of chemoresistant SCLCs.
研究领域:
肿瘤学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2018
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IF 6.042
Ting Hou,Ningning Xu,Wenxiao Wang,Lei Ge,Feng Li
In conventional photoelectrochemical (PEC) analysis, photoactive materials are usually immobilized on electrode surfaces, and such immobilization procedures are tedious and time-consuming, and it is also difficult to prepare electrodes with good reproducibility. To circumvent such limitations, we propose here a truly immobilization-free diffusivity-mediated PEC bionsensing strategy for microRNA assay, using methylene blue (MB) in solution as the photoactive probe, and nonmodified indium tin oxide (ITO) glass as the working electrode. The hybridization between the target microRNA and the MB-labeled single-stranded DNA probe (MB-DNA) triggers the digestion of MB-DNA by T7 exonuclease (T7 Exo), thus to generate MB-labeled mononucleotide, and then the released target microRNA initiates the subsequent cycling processes and generates a large amount of MB-labeled mononucleotides. Due to the diffusivity difference between MB-DNAs and MB-labeled mononucleotides, significantly increased photocurrent signal is observed for MB-labeled mononucleotides as compared to that of MB-DNAs. Therefore, via this “signal-on” mode and the T7 Exo facilitated signal amplification, a facile and highly sensitive immobilization-free PEC microRNA assay is readily realized, with a detection limit down to 27 aM. Moreover, this strategy exhibits excellent specificity and is successfully applied in detecting microRNA spiked in serum samples. Since all the reactions take place in homogeneous solutions and no electrode modification is needed, this PEC biosensing strategy exhibits the advantages of simplicity, rapidness, and good reproducibility. More significantly, it provides a novel concept to design truly immobilization-free PEC biosensing systems, and shows potential to be applied in bioanalysis and biochemical research.
研究领域:
生物分析
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分子生物学
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DOI
高影响因子
Oncotarget
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2017
·
IF 5.168
Hai-Ning Liu,Hao Wu,Yan-Jie Chen,Yu-Jen Tseng,Enkhnaran Bilegsaikhan,Ling Dong,Xi-Zhong Shen,Tao-Tao Liu
Background Many new diagnostic biomarkers have been developed for hepatocellular carcinoma (HCC). We selected two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and attempted to establish appropriate models. Methods We reviewed the diagnostic efficiencies of all microRNAs identified by previous diagnostic tests. Then we chose appropriate microRNAs to validate the diagnostic efficiencies, and determined the optimal combination. We included 66 patients with HCC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was performed, and we used three multivariate statistical methods to establish diagnostic models. The concentration of alpha feto-protein (AFP) was determined for comparison with the novel models. Results 82 published studies and 92 microRNAs were ultimately included in this systematic review. Seven microRNAs were selected for further validation of their diagnostic efficiencies. Among which, miR-21, miR-106b, miR-125b, miR-182 and miR-224 had a significantly different expression in HCC patients. The combination of miR-21, miR-106b and miR-224 had the highest area under the curve (AUC) at 0.950 with a sensitivity of 80.3% and a specificity of 92.7%. The GC/MS analysis exhibited an excellent diagnostic value and the AUC reached 1.0. In comparison, the AUC of the traditional biomarker, AFP, was 0.755. Conclusion MicroRNAs and metabolomics shows promising potential as new diagnostic methods due to their high diagnostic value compared with traditional biomarkers.
研究领域:
肿瘤学
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分子生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2018
·Vol. 19
·期 2
·447
·
IF 3.687
Ze-Qun Jiang,Mu-Han Li,Yue-Mu Qin,Hai-Ying Jiang,Xu Zhang,Mian-Hua Wu
Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC.Keywords:luteolin;apoptosis;non-small cell lung cancer;microRNA-34a-5p
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
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IF 19
Shuang Zhao,Xuesong Wang,Ruijia Deng,Xiaoqi Tang,Zuowei Xie,Ping Huang,Xianlan Wu,Jie Luo,Yu Tang,Jing Sheng,Sha Yang,Ming Chen,Kai Chang
Synthetic catalytic DNAzyme circuits have gained great attention as versatile theranostic toolboxes, but their accuracy and efficiency is restricted by uncontrolled signal leakage and inefficient circuitry activation. Here, a trinity DNAzyme circuit (TriDC) is constructed using a unique logic gate bioswitchable DNA tetrahedral walker@MnO 2 nanosheets structure. The AND logic gate bioswitchable DNA tetrahedral walker, composed of dual allosteric DNAzyme (termed “commander” and “soldier”) and tetrahedral scaffold, is used to execute imaging-guided gene therapy by avoiding undesired signal leakage and cascade “walking” in a confined space. Glutathione-mediated reduction of MnO 2 nanosheets provides secondary confinement to stack the DNA tetrahedral walker in situ, offering abundant Mn 2+ as a cofactor to achieve self-sufficiency of DNAzyme circuits and induce chemo-dynamic therapy. The structure increases local reaction concentrations by ≈100-fold according to the collision frequency model, enabling the AND logic detection of microRNA-10b and microRNA-155 at a limit of detection of 98.97 p m , thereby facilitating the precise imaging of breast cancer cells. The combined gene/chemo-dynamic therapy achieves 66.2% tumor growth inhibition efficiency. The TriDC offers novel insights into tumor theranostics and also presents a paradigm for the in situ implementation of higher-order DNAzyme circuits.
研究领域:
纳米技术
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生物医学工程
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诊疗学
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癌症研究
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分子生物学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2022
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IF 9.221
Qi Wang,Wenyong Li,Juan Xia,Hai Wu,Lijun Wu,Jianguo Xu
The construction of DNA nanodevices is vital for disease diagnosis and biomedical study. Herein, we proposed a ternary DNA nanomachine for microRNA determination using a molecular beacon (MB) coupled Y shape probe (MB-YP). The MB-YP was a tripartite junction scaffold connected with MB-Y I , Y II , and Y III . The target miRNA firstly recognizes MB-Y I , activating the MB-Y I -DNA nanomachine to produce endogenous primer I (EP I ) responsible for the activation of Y II -DNA nanomachine. The Y II -DNA nanomachine then allows the production of numerous EP II , which in turn activates the Y III -DNA nanomachine to produce EP III for re-activating MB-Y I -DNA nanomachine. The stepwise operated MB-Y I -DNA nanomachine, Y II -DNA nanomachine, and Y III -DNA nanomachine constituted the ternary DNA nanomachine and the repeated use of EP I , EP II , and EP III permits it an all-in amplification. These features lead to the opening of MB-Y I for emitting strong fluorescence. As low as 1 fM miRNA can thus be quantitatively detected and the linear response of the miRNA is from 1 fM to 100 pM (six orders of magnitude). Moreover, the nanomachine is specific to distinguish target miRNA from one-base mutant, inserted, and deleted target analogs. Its practicability was demonstrated by confirming miRNA-21 is overexpressed in clinical human serums from lung cancer patients than healthy donors.
研究领域:
生物医学工程
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分子生物学
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纳米技术
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癌症诊断
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产品关联
DOI
高影响因子
MEDICAL SCIENCE MONITOR
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2020
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IF 1.918
Xiaolin Pu,Hua Jiang,Wei Li,Lin Xu,Lin Wang,Yongqian Shu
Background The coatomer protein complex subunit beta 2 (COPB2) gene is upregulated and promotes cell proliferation in some cancer cells. This study aimed to investigate the role of microRNA (miRNA) targeting by COPB2 gene expression in human lung adenocarcinoma cell lines, including NCI-H1975 cells. Material/Methods COPB2 expression in normal human bronchial epithelial cells and lung adenocarcinoma cells was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. NCI-H1975 human lung adenocarcinoma cells were transfected with short-interfering COPB2 (siCOPB2). Cell apoptosis and cell proliferation were evaluated by flow cytometry and Cell Counting Kit-8 (CCK-8) assays, respectively. The transwell assay evaluated cell migration. Targeting of miR-335-3p by COPB2 was predicted using TargetScan 7.2 and verified using a dual-luciferase reporter assay in NCI-H1975 cells. MiR-335-3p mimics were transfected into NCI-H1975 cells. The further functional analysis included detection of protein expression for cyclin D1, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), matrix metallopeptidase 9 (MMP9), Bcl-2, and Bax, to verify the role of miR-335-3p targeting by COPB2 in lung adenocarcinoma cells. Results COPB2 was upregulated in lung adenocarcinoma cells and was a direct target of miR-335-3p mimics. COPB2 knockdown promoted cell apoptosis, inhibited cell migration and proliferation in NCI-H1975 cells. The effects of COPB2 knockdown on NCI-H1975 cells were increased by miR-335-3p mimics, which also further reduced the expression levels of cyclin D1, MMP9, and Bcl-2 and further increased TIMP-1 and Bax by siCOPB2. Conclusions This study showed that COPB2 was the functional target of miR-335-3p in NCI-H1975 human adenocarcinoma cells.
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
Nature Communications
·
2021
·Vol. 12
·期 1
·1-14
·
IF 14.919
Wang Yuqin,Guan Xiaoyu,Zhang Shanyu,Liu Yao,Wang Sha,Fan Pingping,Du Xiaoyu,Yan Shuanghong,Zhang Panke,Chen Hong-Yuan,Li Wenfei,Zhang Daoqiang,Huang Shuo
Folding of RNA can produce elaborate tertiary structures, corresponding to their diverse roles in the regulation of biological activities. Direct observation of RNA structures at high resolution in their native form however remains a challenge. The large vestibule and the narrow constriction of a Mycobacterium smegmatis porin A (MspA) suggests a sensing mode called nanopore trapping/translocation, which clearly distinguishes between microRNA, small interfering RNA (siRNA), transfer RNA (tRNA) and 5 S ribosomal RNA (rRNA). To further profit from the acquired event characteristics, a custom machine learning algorithm is developed. Events from measurements with a mixture of RNA analytes can be automatically classified, reporting a general accuracy of ~93.4%. tRNAs, which possess a unique tertiary structure, report a highly distinguishable sensing feature, different from all other RNA types tested in this study. With this strategy, tRNAs from different sources are measured and a high structural conservation across different species is observed in single molecule.
研究领域:
纳米技术
·
生物物理学
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生物信息学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2025
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IF 4.1
Yinyin Zhao,Binyuan Jiang,Shengnan Zuo
Purpose Cucurbitacins have demonstrated anti-inflammatory effects and show promise for inflammatory bowel diseases. However, the underlying mechanisms by which cucurbitacins affect colitis remain largely unknown.Methods In this study, we investigated the impact of cucurbitacin IIa on dextran sulfate sodium (DSS)-induced colitis in rats and the alterations in intestinal extracellular vesicles (EVs). EVs were isolated and characterized, followed by analysis of the small RNAs and proteins encapsulated within them using small RNA sequencing and proteomics, respectively.Results Our results revealed that cucurbitacin IIa alleviated colitis symptoms in DSS-treated rats, along with changes in the morphology and composition of intestinal EVs. Notably, EVs from cucurbitacin IIa-treated rats also mitigated colitis symptoms in DSS-treated rats. Further analysis showed that cucurbitacin IIa modified the protein profiles and microRNA composition of EVs extracted from the feces of colitis rats. Specifically, microRNA-30b-5p, significantly increased by cucurbitacin IIa, was found to alleviate colitis symptoms in DSS-treated rats. In conclusion, cucurbitacin IIa appears to alleviate colitis by promoting the release of microRNA-30b-5p from host-derived extracellular vesicles.Conclusion These findings enhance our understanding of cucurbitacin IIa’s effects on intestinal health and offer potential new therapeutic targets for inflammatory bowel disease treatment.
研究领域:
药理学
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胃肠病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL PAPERS
·
2024
·Vol. 78
·期 14
·7943-7950
·
IF 2.1
Li Zhigang,Liu Xuzhuo,Wang Chunlong,Song Hanbing,Zhang Jie
In this study, we synthesized zinc selenide (ZnSe)-polyacrylamide (PAM) nanomaterials for their potential application in treating knee osteoarthritis (KOA). Initially, we characterized the newly prepared material through various techniques including Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and nitrogen adsorption–desorption to confirm its identity as the desired product. The results demonstrated that ZnSe-PAM nanomaterial exhibited excellent water solubility, biocompatibility, and stability, along with a large surface area, making it suitable for use as a drug carrier. Subsequently, the material was loaded with the drug 1 to obtain ZnSe-PAM@1. Cellular and thermosensitive experiments were then conducted, revealing that this nanomaterial could facilitate drug release by generating heat, thereby reducing the level of microRNA-146a-5P and blocking the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/extracellular (PI3K/Akt/mTOR/ERK) signal-regulated kinase signaling pathway, thus alleviating the symptoms of KOA. These findings present a new direction for drug intervention in KOA and highlight the potential of developing ZnSe-PAM nanomaterials as novel drug carriers.
研究领域:
材料科学
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医学
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生物技术
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Xiaoqi Tang,Yihui Chen,Binpan Wang,Dan Luo,Jue Wang,Yuan He,Liu Feng,Ying Xu,Shuang Xie,Ming Chen,Kai Chang
Manipulating the expression of cellular genes through efficient CRISPR/Cas9 delivery is rapidly evolving into a desirable tumor therapeutics. The exposure of CRISPR/Cas9 to a complex external environment poses challenges for conventional delivery carriers in achieving responsive and accurate release. Here, we report a Trojan horse-like nanocapsule for the on-demand delivery of CRISPR/Cas9 in a microRNA-responsive manner, enabling precise tumor therapy. The nanocapsule comprises a nanoassembled, engineered DNAzyme shell encasing a Cas9/sgRNA complex core. The DNAzyme, functioning as a catalytic unit, undergoes a conformational change in the presence of tumor-associated microRNA, followed by activating a positive feedback-driven autonomous catabolic cycle of the nanocapsule shell. This catabolic cycle is accomplished through chain reactions of DNAzyme “cleavage–hybridization–cleavage”, which ensures sensitivity in microRNA recognition and effective release of Cas9/sgRNA. Utilizing this Trojan horse-like nanocapsule, as low as 1.7 pM microRNA-21 can trigger the on-demand release of Cas9/sgRNA, enabling the specific editing of the protumorigenic microRNA coding gene. The resulting upregulation of tumor suppressor genes induces apoptosis in tumor cells, leading to significant inhibition of tumor growth by up to 75.94%. The Trojan horse-like nanocapsule, with superior programmability and biocompatibility, is anticipated to serve as a promising carrier for tailoring responsive gene editing systems, achieving enhanced antitumor specificity and efficacy.
研究领域:
生物技术
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纳米技术
·
癌症研究
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基因治疗
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分子生物学
✓ 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）