JOR Spine
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2024
·Vol. 7
·期 4
·e70004
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IF 3.4
Daqian Zhou,Tao Liu,Yongliang Mei,Jiale Lv,Kang Cheng,Weiye Cai,Silong Gao,Daru Guo,Xianping Xie,Zongchao Liu
Background Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes. Methods We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co-expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein–protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT-PCR. Additionally, we predicted miRNAs involved in hub gene co-regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs. Results We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT-PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co-regulation of the hub genes using miRNet prediction: mir-191-5p, mir-20a-5p, mir-155-5p, and mir-124-3p. Using limma difference analysis, we discovered that mir-191-5p, mir-20a-5p, and mir-155-5p were all down-regulated and expressed in IVDD samples, but mir-124-3p showed no significant change. Conclusion JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.
研究领域:
分子生物学
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生物信息学
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骨科医学
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PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2012
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IF 4.555
Sai Bi,Yangyang Cui,Li Li
Considering the great significance of microRNAs (miRNAs) in cancer detection and typing, the development of sensitive, specific, quantitative, and low-cost methods for the assay of expression levels of miRNAs is desirable. We describe a highly efficient amplification platform for ultrasensitive analysis of miRNA (taking let-7a miRNA as a model analyte) based on a dumbbell probe-mediated cascade isothermal amplification (DP-CIA) strategy. The method relies on the circularization of dumbbell probe by binding target miRNA, followed by rolling circle amplification (RCA) reaction and an autonomous DNA machine performed by nicking/polymerization/displacement cycles that continuously produces single-stranded G-quadruplex to assemble with hemin to generate a color signal. In terms of the high sensitivity (as low as 1 zmol), wide dynamic range (covering 9 orders of magnitude), good specificity (even single-base difference) and easy operation (one probe and three enzymes), the proposed label-free assay is successfully applied to direct detection of let-7a miRNA in real sample (total RNA extracted from human lung tissue), demonstrating an attractive alternative for miRNA analysis for gene expression profiling and molecular diagnostics, particularly for early cancer diagnosis.
研究领域:
分子生物学
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医学诊断
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生物化学
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DOI
PubMed
高影响因子
Chemosensors
·
2022
·Vol. 10
·期 7
·276
·
IF 4.229
Kunhan Nie,Yongjian Jiang,Na Wang,Yajun Wang,Di Li,Lei Zhan,Chengzhi Huang,Chunmei Li
The abnormal expression of miRNA is closely related to the occurrence of pancreatic cancer. Herein, a programmable DNAzyme amplifier for the universal detection of pancreatic cancer-related miRNAs was proposed based on its programmability through the rational design of sequences. The fluorescence signal recovery of the DNAzyme amplifier showed a good linear relationship with the concentration of miR-10b in the range of 10–60 nM, with a detection limit of 893 pM. At the same time, this method displayed a high selectivity for miR-10b, with a remarkable discrimination of a single nucleotide difference. Furthermore, this method was also successfully used to detect miR-21 in the range of 10–60 nM based on the programmability of the DNA amplifier, exhibiting the universal application feasibility of this design. Overall, the proposed programmable DNAzyme cycle amplifier strategy shows promising potential for the simple, rapid, and universal detection of pancreatic cancer-related miRNAs, which is significant for improving the accuracy of pancreatic cancer diagnosis.Keywords:DNAzyme amplifier;signal amplification;miRNA detection;pancreatic cancer
研究领域:
分子生物学
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医学诊断
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生物化学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Xiaofang Liu,Qun Wang,Jiawei Li,Zhan Diao,Jingzhou Hou,Danqun Huo,Changjun Hou
Simultaneous detection of multiple breast cancer-associated miRNAs significantly raises the accuracy and reliability of early diagnosis. In this work, disposable carbon fiber paper serves as the biosensing interface, linking DNA probes via click chemistry to efficiently capture targets and signals efficiently. DNA probes have multiple recognition domains that trigger a cascade reaction through the helper probes and targets, resulting in two signals output. The signals are centrally encapsulated in the pore of the MIL-88(Fe)-NH2. The signal carriers are directed by signal probes to the recognition domains that correspond to the DNA probes. The biosensor is selective and stable, and it can quantify miRNA-21 and miRNA-155 simultaneously with detection limits of 0.64 and 0.54 fmol/L, respectively. Furthermore, it demonstrates satisfactory performance in tests conducted with normal human serum and cell lysate. Overall, this method makes a satisfactory exploration to realize an inexpensive and sensitive biosensor for multiple biomarkers.
研究领域:
生物技术
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生物传感器
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癌症研究
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分子生物学
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分析化学
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PubMed
高影响因子
NANOTECHNOLOGY
·
2024
·Vol. 35
·期 46
·465101
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IF 2.9
Hongmei Tang,Xuetao Zhang,Yuyan Bao,Huazhen Shen,Minglan Fan,Yangchen Wang,Siyun Xiang,Xiang Ran
We present an intelligent photothermal therapy agents by functionalizing gold nanoparticles with specific nucleic acid sequences. Hairpin nucleic acids are modified to the nanoparticles, forming AuNPs-1 and AuNPs-2. Upon infiltrating cancer cells, these nanoparticles undergo catalytic hairpin assembly in the presence of target miRNA, leading to aggregation and subsequent photothermal conversion. Under near-infrared laser irradiation, aggregated gold nanoparticles exhibit efficient photothermal conversion, selectively damaging cancer cells. This approach offers heightened selectivity, as nanoparticles only aggregate in environments with cancer biomarkers present, sparing normal cells. Cytotoxicity assays confirm minimal toxicity to normal cells. In vivo studies on mice bearing solid tumors validate the system's efficacy in tumor regression. Overall, this study highlights the potential of nucleic acid-functionalized gold nanoparticles in intelligent and selective cancer photothermal therapy, offering insights for targeted diagnosis and treatment development.
研究领域:
生物医学工程
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分子生物学
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纳米医学
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PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2022
·
IF 9.221
Jiawei Shen,Tingting Li,Min Wang,Bo Yao
MicroRNAs (miRNAs) are a category of short non-coding RNA molecules which play essential roles in regulating gene expression. Correspondingly, the aberrant expression of miRNAs is commonly related to the development of various diseases including cancers and cardiovascular diseases. Hence, miRNA is considered as an ideal biomarker for disease diagnosis and its quantification is highly demanded. Herein, an isothermal and enzyme-free miRNA assay based on catalytic hairpin assembly (CHA) amplification coupled with inductively coupled plasma mass spectrometry (ICP-MS) detection is proposed. Two hairpin probes are employed in CHA reaction with rare earth element tag on H1 for ICP-MS detection and biotin on H2 for immobilization on magnetic beads. In the presence of target miRNA, the two independent probes open up their stem-loop structure and hybridize. The target miRNA will be released after the hybridization to trigger another CHA reaction. Ultimately, one target miRNA molecule promotes a number of CHA cycles and produces several copies of hybridized complex leading to the enhanced ICP-MS signal. Based on this approach, miRNA-141 was successfully analyzed with high sensitivity and specificity. The limit of detection (LOD) was 88 fmol with a linear range 0.1–2 pmol. Compared with fluorescence mediated CHA method and ICP-MS mediated basic sandwich method, the current strategy displayed the lowest LOD. The developed method was also applied to analyze miRNA-141 and miRNA-21 simultaneously to demonstrate its multiple detecting capability and practical applicability. Furthermore, this miRNA assay has the potential to become a high-throughput method by employing more distinct rare earth elements.
研究领域:
分子生物学
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分析化学
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生物医学工程
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癌症研究
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心血管疾病
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高影响因子
PLANT CELL
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2026
·Vol. 38
·期 3
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IF 13.5
Fang Yixiao,Li Ning,Fan Youhong,Zhang Zhenye,Cai Yuchen,Guo Mengwei,Yang Lin,Jiang Shipeng,Zheng Binglian,Mei Jun,Ren Guodong
The intracellular accumulation of microRNAs (miRNAs) is dynamically controlled at multiple levels, including transcription, processing, and degradation. However, the molecular mechanisms of miRNA turnover and active degradation remain understudied. Here, we delineated the global small RNA turnover landscape in Arabidopsis thaliana, using transcription inhibition combined with NaIO4 oxidative small RNA sequencing (OX-sRNA-seq), which specifically captures 2′-O-methylated small RNAs. We also employed a nontoxic pulse-chase approach based on metabolic RNA labeling to corroborate these results. Our results showed that although most miRNAs and small interfering RNAs (siRNAs) are highly stable, a subset of miRNAs undergo rapid turnover. In contrast, the majority of miRNA*s are short-lived. Reverse genetic analysis further demonstrated that ARGONAUTE 1 (AGO1) and HUA ENHANCER 1 (HEN1) act in maintaining miRNA stability. Intriguingly, we found that HAWAIIAN SKIRT (HWS), a pivotal player in target mimicry induced miRNA degradation, is crucial for the degradation of short-lived miRNAs. Plants utilize both transcription shutoff and HWS-mediated miR398 clearance during oxidative stress responses. Furthermore, HWS is required to maintain miR399 homeostasis under phosphate-sufficient conditions and accelerate its degradation after prolonged starvation. Together, our results shed light on the dynamics and mechanisms of miRNA stability in plants.
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PubMed
高影响因子
Communications Chemistry
·
2026
·
IF 6.9
Guo Yiqun,Zhang Jingkun,Jiang Liangyu,Yin Huamei,Niu Xiankai,Shen Liang,Guo Yuna,Li Yuancheng
Recent advances in molecular diagnostics have highlighted the transformative potential of multi-protein response logic gates in enhancing sensitivity and specificity for cancer detection. However, logic gates based on multi-type nucleic acid responses remain underexplored. In this study, we present a dual-biomarker response platform that utilizes nucleic acid logic gates targeting miR-21 ( microRNA-21 ) and lncRNA MALAT1 ( metastasis-associated lung adenocarcinoma transcript 1 ). Compared to traditional single-target methods, our platform effectively overcomes common challenges, such as expression variability and cross-reactivity, which are inherent in single biomarker approaches, thereby significantly improving both diagnostic sensitivity and specificity. This platform is based on rolling circle amplification (RCA) technology and incorporates two key components: a primer switch and a padlock probe switch. When miR-21 is recognized, a hairpin probe undergoes a shape change, releasing a primer that starts the RCA process. Simultaneously, a MALAT1 -specific padlock probe forms a closed circular structure, which is necessary to activate RCA and increase signal detection. Furthermore, the RCA products contain G-quadruplex sequences that can bind to hemin, forming DNAzymes that produce an electrochemical signal. This strategy significantly enhances diagnostic sensitivity and specificity, demonstrating strong potential for early cancer detection and precision oncology.
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高影响因子
ANALYTICA CHIMICA ACTA
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2026
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IF 6.1
Dan Qin,Shijin Zhou,Davaasuren Tsendjav,Jing Li,Jinming Kong
Background The early and accurate detection of miRNA-21 is of great significance for both lung cancer diagnosis and livestock health monitoring, given its conserved sequence across mammals. Herein, we report an enzyme-free electrochemical biosensor based on surface-initiated ring-opening metathesis polymerization (ROMP) for the ultrasensitive detection of miRNA-21. A thiolated peptide nucleic acid (PNA) probe was immobilized on a gold electrode to capture the target. The formed PNA–RNA hybrid duplex provided a high-density phosphate backbone that served as a coordination anchor for Zr(IV) ions, enabling directional immobilization of acrylic acid monomers via Zr–O–P/Zr–O–C bridges. Subsequent addition of a water-soluble ruthenium catalyst (AquaMet) initiated in situ ROMP of cyclopentenyl ferrocene (CFc) monomers, converting a single hybridization event into long polymer chains densely decorated with electroactive ferrocene units for substantial signal amplification. Results Under optimized conditions, the biosensor exhibited a wide linear range from 0.1 fM to 0.1 nM, with an ultralow detection limit of 67 aM. It showed excellent selectivity against single-base mismatches, as well as good reproducibility and storage stability. Importantly, the sensor maintained satisfactory recovery rates in diluted human serum and demonstrated strong anti-interference capability in complex matrices. Significance Owing to the sequence conservation of miRNA-21 across mammals and the mild, enzyme-free nature of the ROMP strategy, this platform holds great potential for both clinical lung cancer screening and on-site health monitoring in livestock and poultry.
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
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IF 7.7
Mengyi Tian,Youqiang Xing,Wei Wang,Ze Wu,Peng Huang,Bingjue Li,Lei Liu
Accurate detection of microRNA concentrations is essential for early cancer diagnosis and monitoring. Existing methods typically provide a linear response within a limited concentration range, which hinders their precise clinical application. This study presents a novel sensing approach using the fluorescence properties of nitrogen vacancy (NV) centers. Magnetic particles capture and enrich fluorescent nanodiamonds (FNDs), and effectively address signal inconsistencies due to variations in FND particles by applying a voltage that regulates the NV center fluorescence. Our method achieves a linear response to microRNAs across a broad concentration range (10 fM to 1 μM), with the determination coefficient (R²) of the fluorescence signal, enhanced from 0.8711 to 0.9951 through voltage modulation. Additionally, optimizing experimental conditions and enhancing FND fluorescence increased the signal intensity, achieving a minimum detection limit of 7.17 fM. The combination of sensitive detection and an extensive linear range suggests the potential of this strategy as a universal detection method for the early diagnosis of various diseases.
研究领域:
生物医学工程
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分子生物学
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量子传感
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高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2025
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IF 4.6
Pengnan Yao,Nan Ma,Jinming Kong,Gengzhi Sun,Xueji Zhang
MicroRNAs (miRNAs) are a class of endogenous, non-coding, single-stranded RNA molecules that are typically 20–25 nucleotides in length. The expression levels of miRNAs in blood, tissue, and other samples are characteristically altered in several disease states. The detection of miRNAs represents a promising avenue for the early diagnosis of various diseases. Consequently, there is a clear need to enhance the sensitivity of miRNA detection to facilitate more accurate disease detection. A fluorescent biosensor was developed that utilizes supramolecular host-guest interactions for assembly and Mo-based materials to initiate a reversible addition-fragmentation chain transfer polymerization (RAFT). The scheme functions by modifying the miRNA on Fe 3 O 4 -magnetic nanoparticles (Fe 3 O 4 -MNPs), followed by linking the initiator of the subsequent RAFT reaction through supramolecular host-guest interaction. Ultimately, polymerization reactions initiated by Mo compounds result in the formation of polymers with fluorescent monomers on Fe 3 O 4 -MNPs. The sensor is extremely sensitive and the detection limit of this sensor is 0.03 fM. Furthermore, the protocol has been demonstrated to be highly effective in the detection of samples in serum, which also serves to illustrate the potential of this fluorescent biosensor for the detection of other kinds of miRNAs.
研究领域:
生物化学
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分子生物学
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纳米技术
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分析化学
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生物传感器
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PubMed
高影响因子
MICROCHIMICA ACTA
·
2026
·Vol. 193
·期 2
·74
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IF 5.3
Chang Ruimiao,Liu Shumian,Wang Jingjing,Wang Huichun,Jia Shuai,Ye Yuting,Qu Xinying,Li Yong,Zheng Ji,Fang Xiaoxing
We developed a highly sensitive electrochemical sensor based on zirconium-iron metal-organic frameworks (ZrFe-MOF) for the precise detection of ultra-low abundance miRNA-21. The construction of this sensor, through an innovative thermal alkaline activation strategy, exposed abundant binding sites on the surface of ZrFe-MOF, significantly improving aptamer (Apt) loading efficiency, thereby, achieving unprecedented sensitivity with a wide linear range (100 aM-10 nM, R² = 0.997) and a record-low detection limit of 19.33 aM - outperforming existing methods by 1-2 orders of magnitude. Besides, the biosensor successfully discriminates miRNA-21 expression profiles in breast cancer cell lines and breast adenocarcinoma (MDA-MB-231 vs. MCF-7 vs. MCF-10 A), showing high consistency with qPCR results. This work not only demonstrates a novel binding-site engineering strategy for nucleic acid detection but also presents a clinically viable platform for early cancer diagnosis with superior sensitivity, specificity, and reproducibility. This thermal-alkaline activation strategy could be extended to other bimetallic MOFs for multiplex miRNA detection, with future efforts targeting sensor miniaturization for point-of-care use. Current challenges include balancing the material’s electron transfer efficiency with long-term storage stability and verifying the sensor’s performance in large-scale clinical cohort samples.
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高影响因子
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