JOURNAL OF PHARMACY AND PHARMACOLOGY
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2024
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IF 2.8
Liu Shilan,Liu Xiao,Yang Qinghui,Zeng Chunhua,Hu Gang,Ren Bochen
ObjectivesLung cancer is one of the malignant tumors that threaten human health seriously. Long non-coding RNA (lncRNA) is an important factor affecting tumorigenesis and development. However, the mechanism of lncRNA in lung cancer progression remains to be further explored.MethodsIn this study, the TCGA database was analyzed, and LINC01572 was found to be increased in lung adenocarcinoma (LUAD) tissues. Thereafter, with the help of databases including lncBase, TargetScan, and mirDIP, as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, LINC01572/miRNA-338-5p/TTK regulatory axis and downstream p53 signaling pathway were excavated. qRT-PCR was adopted to detect levels of LINC01572, miRNA-338-5p, and TTK in LUAD cells. The role that LINC01572 played in LUAD cells was validated by CCK-8 assay, flow cytometry, colony formation, Transwell, and scratch healing assays. The binding ability between LINC01572/TTK and miRNA-338-5p was then verified by dual-luciferase and RIP analysis.Key findingsThe results of this study demonstrated that LINC01572 was elevated in LUAD cells compared with normal cells. The overexpression of LINC01572 promoted the proliferative and migratory properties of LUAD cells but inhibited cell apoptosis. The inhibition of LINC01572 resulted in the opposite result. In addition, rescue experiments revealed that LINC01572, as a molecular sponge of miRNA-338-5p, targeted TTK to manipulate p53 for facilitating LUAD cell malignant progression. Apart from this, we constructed a mouse xenograft model and confirmed that the knockdown of LINC01572 hindered the growth of LUAD solid tumors in vivo.ConclusionsOur findings illuminated the molecular mechanism of LINC01572 influencing LUAD and provided new insights for targeted therapy of LUAD cells.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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基因组学
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细胞生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Haikun Luo,Zhao Wang,Qian Mo,Jianying Yang,Fan Yang,Yujin Tang,Jia Liu,Xinchun Li
Intelligent stimulus-responsive theranostic systems capable of specifically sensing low-abundance tumor-related biomarkers and efficiently killing tumors remain a pressing endeavor. Here, we report a multifunctional framework nucleic acid (FNA) nanosystem for simultaneous imaging of microRNA-21 (miR-21) and combined chemo/gene therapy. To achieve this, two FNA nanoarchitectures labeled with Cy5/BHQ2 signal tags were designed, each of which contained an AS1411 aptamer, two pairs of DNA/RNA hybrids, a pH-sensitive DNA catcher, and doxorubicin (DOX) intercalating between cytosine and guanine in the tetrahedral DNA nanostructure (TDN). In the acidic tumor microenvironment, the DNA catchers spontaneously triggered to form an i-motif and create an FNA dimer (dFNA) while releasing DOX molecules to exert a cytotoxic effect. In addition, the overexpressed miR-21 in tumor cells dismantled the DNA/RNA hybrids to produce vascular endothelial growth factor-associated siRNA via a toehold-mediated strand displacement reaction, thus enabling a potent RNA interfering. Also importantly, the liberated miR-21 could initiate cascade-reaction amplification to efficiently activate the Cy5 signal reporters, thereby realizing on-site fluorescence imaging of miR-21 in living cells. The exquisitely designed FNA-based nanosystem showed favorable biocompatibility and stability as well as acid-driven DOX release characteristics. Owing to the aptamer-guided targeting delivery, specific uptake of the FNA-based theranostic nanosystem by HepG2 cells was verified with confocal laser scanning microscopy and flow cytometry analyses, which therefore resulted in apoptosis of HepG2 cells while doing minimal damage to normal H9c2 and HL-7702 cells. Strikingly, both in vitro and in vivo experiments demonstrated the achievements of the FNA-enabled miR-21 imaging and synergistically enhanced chemo/gene therapy. This work thus represents a noteworthy advance on the FNA-based theranostic strategy that can effectively avoid the undesirable premature leakage of anticarcinogen and off-target of siRNA, and achieve on-demand reagents release for tumor diagnostics and treatment.
研究领域:
癌症研究
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纳米技术
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分子生物学
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诊疗学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2024
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IF 5.7
Xinli Wang,Hongyan Liu,Shaoqiang Zhang,Zhongcui Jing,Changkai Zhang,Songxia Yan,Hong Zhou,Haiyan Wang
Background Recently, various techniques have been developed to accurately and sensitively detect tumor biomarkers for the early diagnosis and effective therapy of cancer. The electrochemiluminescence (ECL) method holding outstanding features including high sensitivity, ease of operation, and spatiotemporal controllability exhibited great potential for DNA/RNA detection, immunoassay, cancer cell detection, and environmental analysis. However, a glaring problem of ECL approaches is that the layer-by-layer modification on the electrode leads to poor stability and sensitivity of the sensors. Therefore, new simple and efficient methods for electrode modification which can effectively improve the ECL signal have attracted more and more research interests. Results Based on the dual amplification strategy of target-induced CHA and nanocomposite probes leading to self-generated co-reactant (H 2 O 2 ), we proposed a highly sensitive miRNA-ECL detection system. The introduction of the target miRNA-21 triggers the CHA cycle amplification of DNA1 and biotin-modified DNA2, releasing the target miRNA-21 sequence for the target cycle reaction. After the reaction, the newly introduced DNA2 was combined with Au NPs modified with SA and Glucose oxidase (GOD). In the presence of oxygen, glucose was decomposed by GOD to produce H 2 O 2 , and then H 2 O 2 was immediately catalyzed by the Hemin/G-quadruplex at the double-stranded end of the CHA product to produce a large amount of O 2 −• . As a co-reactant of luminol, the ECL signal was significantly enhanced, thereby achieving highly sensitive detection of miRNA-21 content and obtaining a low detection limit of 0.65 fM. The high specificity of the ECL biosensor was also proved by base mismatch. Significance Compared with other current detection methods, this sensor can achieve quantitative analysis of other target analytes by flexibly changing the probe DNA sequence, and provide a new feasible solution for the detection of tumor-associated markers. Benefiting from the improved sensitivity and selectivity, the proposed biosensing platform is expected to provide a new strategy for biomarkers analysis and outstanding prospect for further clinical application.
研究领域:
生物医学工程
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分析化学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Nanomaterials
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2022
·Vol. 12
·期 11
·1787
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IF 5.719
Zhou Ding,Yue He,Hongtao Rao,Le Zhang,William Nguyen,Jingjing Wang,Ying Wu,Caiqin Han,Christina Xing,Changchun Yan,Wei Chen,Ying Liu
In this paper, a novel rare-earth-doped upconverted nanomaterial NaYF4:Yb,Tm fluorescent probe is reported, which can detect cancer-related specific miRNAs in low abundance. The detection is based on an upconversion of nanomaterials NaYF4:Yb,Tm, with emissions at 345, 362, 450, 477, 646, and 802 nm, upon excitation at 980 nm. The optimal Yb3+:Tm3+doping ratio is 40:1, in which the NaYF4:Yb,Tm nanomaterials have the strongest fluorescence. The NaYF4:Yb, Tm nanoparticles were coated with carboxylation or carboxylated protein, in order to improve their water solubility and biocompatibility. The two commonly expressed proteins, miRNA-155 and miRNA-150, were detected by the designed fluorescent probe. The results showed that the probes can distinguish miRNA-155 well from partial and complete base mismatch miRNA-155, and can effectively distinguish miRNA-155 and miRNA-150. The preliminary results indicate that these upconverted nanomaterials have good potential for protein detection in disease diagnosis, including early cancer detection.Keywords:upconversion nanomaterials;novel fluorescent probe;miRNA-155;miRNA-150
研究领域:
生物医学
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纳米技术
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癌症诊断
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2017
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IF 6.32
Feichi Hu,Jiying Xu,Yi Chen
MicroRNA (miRNA) is a promising new type of biomarkers but at a low fM level and hard to be analyzed. Herein proposed is an innovated surface plasmon resonance imaging (SPRi) method merged with a novel in-plane and vertical signal amplification strategy, that is, orthogonal signal amplification to enable a direct determination of sub-fM miRNA-15a (a multiple tumor diagnostic biomarker). The core idea is to add more mass on a target sample spot first along the surficial direction, then upward from the surface. In detection of miRNA, this was realized by coupling a miRNA-initiated surficial cyclic DNA–DNA hybridization reaction with a DNA-initiated upward cyclic polymerization reaction. A perfect SPRi sensing chip with isolated gold islands bordered by hydrophobic CYTOP was fabricated and used to obtain high-quality chip with low fabrication difficulty. As a result, SPRi contrast largely increases, able to reach a limit of detection and limit of quantification down to 0.56 and 5fM for miRNA-15a, about 107-fold improvement of sensitivity compared with a common SPRi detection. The method could quantify standard miRNA-15a spiked in human serum with an ideal recovery ranging from 98.6% to 104.9% and was validated to be applicable to the direct determination of miRNA-15a in healthy and cancer human serums. The orderly and controllable in situ sensitizing strategy is powerful and readily extendable to detection of other miRNAs.
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
Diagnostics
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2022
·Vol. 12
·期 2
·239
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IF 3.992
Yingying Xie,Wenwen Chen,Mengqian Zhao,Yuhai Xu,Hao Yu,Jianhua Qin,Hongjing Li
Arthritis is caused by inflammation, infection, degeneration, trauma, or other factors that affect approximately 250 million people all over the world. Early diagnosis and prediction are essential for treatment. Exosomes are nanoscale vesicles that participate in the process of joint disease. Serum is the mainly used sources in the study of arthritis-related exosomes, while whether serum exosomes can reflect the contents of synovial fluid exosomes is still unknown. In this work, we separated exosomes from serum and the synovial fluid of osteoarthritis patients and compared their miRNA expression utilizing miRNA sequencing. The results revealed that 31 upregulated and 33 downregulated miRNAs were found in synovial fluid compared to serum. Transcriptome analysis showed that these differentially expressed miRNAs were mainly associated with intercellular processes and metabolic pathways. Our results show that serum-derived exosomes cannot fully represent the exosomes of synovial fluid, which may be helpful for the study of joint diseases and the discovery of early diagnostic biomarkers of arthritis.Keywords:exosomes;miRNA;synovial fluid;arthritis
研究领域:
生物标志物发现
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分子生物学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yaxue Jia,Siqi Zhao,Anping Wang,Jing Huang,Jinlan Yang,Li Yang
A target-induced multiregion MNAzyme nanowire system is designed for the ultrasensitive and homogeneous detection of microRNAs (miRNAs). miRNA-21 and miRNA-375 are chosen as analytes, and a miRNA-induced primer exchange reaction (PER) is utilized to construct a long DNA strand with repetitive sequences. This innovative design enables the efficient anchoring of numerous MNAzymes. This unique architecture significantly boosts the effective local concentration of MNAzymes, thereby enhancing the sensitivity and efficiency of miRNA detection. Notably, the limit of detection (LOD) achieved with our target-induced multiregion MNAzyme nanowire approach is over an order of magnitude lower than most other MNAzyme-based methods, while the MNAzyme reaction time is reduced from several hours to 50 min. The method has demonstrated successful applications in quantitatively determining the expression levels of two miRNAs in cell lysates of MCF-7, HeLa and MCF-10 A cells, highlighting its potential for assaying miRNA biomarkers in clinical samples.
研究领域:
分子生物学
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生物化学
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诊断学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2024
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IF 6.7
Mengxin Zhang,Yingyu Zhang,Xianwei Zhang,Kangbo Liu,Lifeng Li,Zhidan Yu,Jingya Yuan,Wancun Zhang
Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1AP). Subsequently, miRNA-21 facilitates the hybridization of activated H1AP on tFNA-H1AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1AP at the vertices of tFNA-H1AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The AND-gated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.
研究领域:
生物化学
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分子生物学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2021
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IF 7.991
Xiqi Ma,Xiaojuan Wang,Cai Liu,Baosheng Ge,Hua He,Qi Dai,Zhixiong Zhang,Jinyi Yu,Werner M. Nau,Fang Huang
Compared with primary and local tumor, metastasis is more difficult to resect completely and remain the leading cause of death associated with solid tumors. It is therefore pressing to develop effective strategies to prevent and suppress tumor metastasis in its early stages. Heparanase overexpression is significantly associated with increased malignancy and metastasis. Here, we develop a novel heparanase degradable heparin-based microcarrier, HBMA, for specific staining, targeting, and inhibiting tumor cells with high metastatic potential. HBMA is fabricated through self-assembling of three components, positively charged fluorescent gold nanoclusters (KG-AuNCs), heparin polymers (HP), and antisense miRNA-21 oligonucleotides (AM-21), with each component playing multiple roles. Results of confocal microscopy and flow cytometry show that this agent has an excellent capability to label metastatic tumor cells with high selectivity. On the therapeutic side, the results of cell viability assay, wound healing assay, and plate colony formation assay verify that HBMA induces a significant inhibition effect towards the proliferation and migration of the selectively target tumor cells. The heparanase responsive AM-21 delivery, the specific staining, and the efficient tumor cell activity suppression highlight HBMA as a promising cancer theranostic agent to prevent tumor metastasis.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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DOI
高影响因子
Science China-Chemistry
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2020
·Vol. 63
·期 5
·731-740
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IF 6.356
Wang Yingfei,Li Yuyi,Zhang Yue,Ren Kewei,Ju Huangxian,Liu Ying
Array based detection techniques with fluorescence signal reading is a powerful tool for multiple targets analysis. However, when applied fluorescence array for microRNA detection, time-consuming multi-steps surface signal amplification is usually required due to the low abundance of microRNA in total RNA expressions, which impairs detection efficiency and limits its application in point of care test (POCT) manner. Herein, DNA cascade reactors (DCRs) functionalized photonic crystal (PC) array was fabricated for express and sensitive detections of miRNA-21 and miRNA-155. DCRs were assembled by interval conjugation of self-quenched hairpin DNA probes to single strand DNA nanowire synthesized by rolling circle amplification, which generated cascade DNA hybridization reactions in response to target miRNA with instant fluorescence recovery signal. PC array patterns with multi-structure colors further amplified fluorescence with their respective photonic bandgaps (PBGs) matching with the emission peaks of fluorescence molecules labelled on DCRs. The as-prepared DCRs functionalized PC array demonstrated express and sensitive simultaneous detections of miRNA-21 and miRNA-155 with hundreds fM detection limits only in 15 min, and was successfully applied in fast quantifications of low abundance miRNAs from cell lysates and spiked miRNAs from human serum, which would hold great potential for disease diagnosis and therapeutic effect monitoring with a POCT manner.
研究领域:
分子生物学
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纳米技术
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生物医学工程
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临床诊断
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产品关联
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Minghui Wang,Qiaolin Guo,Zhenyong Hu,Yue He,Lai Zhang,Cuifei Chen
An ultrasensitive biosensor has been developed for miR-375 detection. • HRP is embedded into COFs to form stable HRP@COFs co-precipitated nanospheres. • The HRP@COFs preserved enzymatic activity and enhanced catalytic efficiency. • The biosensor has been successfully validated using clinical samples. The dysregulated expression of microRNA (miRNA) in various cancers has attracted considerable attention owing to their crucial roles in tumor initiation and progression. Among them, miR-375 has been recognized as a prospective biomarker for early malignancy detection and therapeutic monitoring. In this study, a highly sensitive electrochemical biosensor has been developed based on horseradish peroxidase (HRP)-embedded covalent organic framework (HRP@COFs) co-precipitated nanospheres for the detection of miR-375. The HRP@COFs nanocomposite effectively preserves the enzymatic activity of HRP while providing the structural stability and high loading capacity of COFs, thereby enhancing catalytic efficiency and signal amplification. In the presence of target miR-375, the azide-modified H1 hairpin probes on the HRP@COFs surface are activated, leading to the formation of a rigid H1-H2 duplex structure through competitive hybridization with H2 hairpins. The resulting H2-H1-HRP@COFs complexes are subsequently anchored onto the electrode surface via click chemistry. Upon the addition of H 2 O 2 , HRP catalyzes aniline polymerization and deposition, resulting in a significant electrochemical response. This biosensor achieves ultrasensitive detection of miR-375 with a detection limit as low as 230 aM. It has been successfully validated using clinical samples, demonstrating great potential for reliable breast cancer diagnosis. This work highlights the synergistic advantages of integrating HRP with COFs, providing a robust and efficient platform for microRNA detection and expanding the applications of COFs-based materials in biosensing and clinical diagnostics. Download: Download high-res image (151KB) Download: Download full-size image
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DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2012
·
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
危险品化学品经营许可证（带存储）