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.
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高影响因子
ACS Applied Nano Materials
·
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.
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高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2020
·Vol. 475
·期 1
·1-13
·
IF 2.795
Lin Lin,Xin Bing,Jiang Tao,Wang Xin-lu,Yang Hua,Shi Tie-mei
Long non-coding RNAs are associated with the pathogenesis of cancers. Moreover, LINC00460 is involved in the development of multiple cancers. However, the function of LINC00460 in cervical cancer (CC) remains inconclusive. Herein, CC tissues and tumor-adjacent tissues were collected from patients. The effect of LINC00460 silencing in cell proliferation and apoptosis in CC was explored in vitro and in vivo. Additionally, the interaction between LINC00460 and miR-503-5p was analyzed using dual luciferase reporter assay. The expression of genes and proteins was assayed using quantitative real-time PCR, western blotting and immunohistochemistry, cell viability using MTT assay, cell cycle distribution using flow cytometry, cell apoptosis using Annexin V staining, Hoechst staining and TUNEL assay. LINC00460 levels in CC tissues were higher than tumor-adjacent tissues. LINC00460 silencing suppressed proliferation and promoted apoptosis of CC cells as evidenced by decreased cell viability, inhibited proliferation-related protein and cell cycle protein expressions and G1/S transition, increased apoptotic cells and Hoechst-positive cells, and enhanced apoptosis-related protein expressions. LINC00460 could bind to miR-503-5p and LINC00460 silencing enhanced miR-503-5p expression and inhibited its target gene expressions in CC cells. MiR-503-5p inhibition reversed LINC00460 silencing-caused inhibition of cell proliferation and miR-503-5p target gene expressions, and promotion of cell apoptosis. LINC00460 silencing also attenuated tumor growth, promoted miR-503-5p levels and cell apoptosis, and inhibited cell proliferation and miR-503-5p target gene expressions in tumor tissues. Hence, LINC00460 functioned as an oncogene in CC that affected cell proliferation and apoptosis via sponging miR-503-5p. This study provides a novel therapeutic target for CC.
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DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2020
·Vol. 413
·期 2
·543-553
·
IF 3.637
Wang Dongwei,Wang Jiasheng,Song Zhiling,Hui Ni
Ultrasensitive and low-fouling microRNA electrochemical biosensors were successfully constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. For the three kinds of antifouling materials investigated, the newly designed and synthesized peptide exhibited superior antifouling ability to others, and it could effectively reduce the nonspecific adsorption of proteins and even prevent the fouling effect of serum. Compared with microRNA biosensors without antifouling capability, or those modified with polyethylene glycol or mercapto alcohol, the biosensor modified with the designed zwitterionic peptide showed the highest specificity for single-base mismatch, three-base mismatch, and completely complementary microRNAs. Most interestingly, the experimental results indicated that the introduction of antifouling molecules to the sensing interfaces did not significantly change the sensitivity of the biosensor. The strategy of constructing antifouling biosensors based on newly synthesized zwitterionic peptides and conducting polymers can be promisingly extended to the development of other electrochemical sensors and biosensors without encountering biofouling.
Ultrasensitive and low-fouling microRNA electrochemical biosensors were constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. The biosensor modified with the designed zwitterionic peptide showed the highest specificity amongst four kinds of biosensors.
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PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2020
·Vol. 20
·期 6
·1-1
·
IF 1.785
Tongtong Niu,Yan An,Tingting Lv,Dongning Liu
Diabetic retinopathy (DR) is a serious complication of diabetes and the most common metabolic disorder. Recently, long non‑coding (lnc)RNAs have been identified as critical regulators of DR. Ribosomal protein SA pseudogene 52 (RPSAP52) is an oncogenic lncRNA expressed in pituitary tumors. The present study aimed to investigate the functions of RPSAP52 in DR. RPSAP52 levels in the plasma of diabetic patients with or without DR complication was detected. Luciferase reporter assays, RT‑qPCR and western blotting were performed to detect the interaction between RPSAP52 and micro RNA (miR)‑365. Moreover, expression vectors of RPSAP52 and Timp3, as well as miR‑365 mimics were transfected into ARPE‑19 cells exposed to high glucose and the apoptotic cells were detected. The results showed that RPSAP52 was downregulated in patients with DR compared with patients with diabetes without obvious complications. RPSAP52 directly interacted with miR‑365, while overexpression of RPSAP52 and miR‑365 did not affect the expression of one another. In addition, overexpression of RPSAP52 upregulated TIMP metallopeptidase inhibitor 3 (Timp3) in retinal pigment epithelial (RPE) cells. High glucose treatment led to downregulated RPSAP52 and Timp3, but upregulated miR‑365 in RPE cells. Moreover, cell apoptosis analysis identified that overexpression of RPSAP52 and Timp3 led to a decreased apoptotic rate of RPE cells under high glucose treatment. Therefore, it was speculated that RPSAP52 may upregulate Timp3 by serving as the endogenous sponge of miR‑365 in DR to suppress RPE cell apoptosis.
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PubMed
高影响因子
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
·
2020
·Vol. 37
·期 2
·111-120
·
IF 1.737
Shi Liu,Ying Gong,Xue-Dong Xu,Hui Shen,Shuai Gao,Hai-Dong Bao,Shi-Bin Guo,Xue-Feng Yu,Jian Gong
Gastric cancer is one of the most common cancers globally and has a poor prognosis. MiR-936 has been reported to regulate cell activity and tumor progression in non-small cell lung cancer, glioma, and epithelial ovarian cancer. However, the specific role and mechanism of miR-936 in gastric cancer have not been explored. In present study, gastric cancer cells were transfected with miR-936 mimic, and cell proliferation, cell cycle distribution, cell apoptosis, migration and invasion were assessed via cell-counting kit-8, flow cytometry, wound healing, and transwell assay, respectively. Dual luciferase reporter assay was used to check miR-936 binding to its downstream target. It was shown that miR-936 was downregulated in gastric cancer tissues and cells. Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4) was confirmed as a direct target of miR-936 and negatively regulated its expression by miR-936. Overexpression of miR-936 suppressed cell proliferation, cell cycle progression, cell migration and invasion, and enhanced cell apoptosis in gastric cancer cells, which could be reversed by further ERBB4 overexpression. Western blot results showed that miR-936/ERBB4 axis regulated Akt-related pathways to control gastric cancer cell activities. Therefore, our data suggest that miR-936 overexpression inhibits cell proliferation and invasion and promotes cell apoptosis through Akt-related pathways by targeting ERBB4, which provides novel insight to target miR-936 or miR-936/ERBB4 axis for the treatment of gastric cancer.
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PubMed
高影响因子
Small
·
2020
·Vol. 16
·期 19
·2000460
·
IF 11.459
Manshu Peng,Feifei Sun,Na Na,Jin Ouyang
Nanogap antennas are plasmonic nanostructures with a strong electromagnetic field generated at the gap region of two neighboring particles owing to the coupling of the collective surface plasmon resonance. They have great potential for improving the optical properties of fluorophores. Herein, nanogap antennas are constructed using an aqueous solution-based method to overcome the defects of weak fluorescence and photobleaching associated with traditional organic dyes, and a highly sensitive nanogap antenna-based sensing strategy is presented for the detection of low-abundance nucleic acid biomarkers via a target-triggered strand displacement amplification (SDA) reaction between two DNA hairpins that are tagged to the tips of gold nanorods (Au NRs). In the presence of targets, end-to-end Au NR dimers gradually form, and the fluorophores quenched by the Au NRs exhibit a dramatic fluorescence enhancement due to the plasmon-enhanced fluorescence effect of nanogap antennas. Meanwhile, the SDA reaction results in secondary amplification of fluorescence signals. Combined with single-molecule counting, this method applied in miRNA-21 detection can achieve a low detection limit of 97.2 × 10 −18 m . Moreover, accurate discrimination between different cells through miRNA-21 imaging demonstrates the potential of this method in monitoring the expression level of low-abundance nucleic acid biomarkers.
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PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Yujing Liang,Yifei Wang,Mengdi Yu,Yuqian Jiang,Jinhua Shang,Xiaoqing Liu,Fuan Wang
Biomolecules play essential roles in regulating the orderly progression of biochemical reaction networks. DNA-based biocircuits supplement an attractive and ideal approach for the visual imaging of endogenous biomolecules, yet their sensing performance is commonly encumbered by the undesired signal leakage. To solve this issue, here we proposed a glutathione (GSH)-activated DNA circuit for achieving the spatio-selective microRNA imaging through the successive response of a GSH-specific activation procedure and a non-enzymatic catalytic signal amplification procedure. In this design, by incorporating a disulfide bond into the pre-sealed nucleic acid probe, the uncontrolled circuitry leakage could be effectively ameliorated. In target cancer cells with high-abundant GSH and miR-21, endogenous GSH recognized and cleaved the pre-installed disulfide bond within DNA probes, thereby restoring the activity of circuitry components. The miR-21 then catalyzed the specific operation of circuitry for generating an amplified readout signal. We demonstrate that this system not only enables the effective discriminations of various cell types, but also contributes to the exploration of the correlationship between GSH and miR-21. This on-site activated DNA circuit can be extended to the robust analysis and exploration of different biomolecular interactions, offering a reliable reference for the in-depth understanding of biochemical interaction networks.
研究领域:
生物化学
·
分子生物学
·
医学诊断
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PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Xiangdan Meng,Kai Zhang,Fan Yang,Wenhao Dai,Huiting Lu,Haifeng Dong,Xueji Zhang
MicroRNAs (miRNAs) are involved in the essential progresses of many diseases and have emerged as therapeutic and diagnostic biomarkers. The combination of miRNA aberrant expression and tumor microenvironment (TME) features holds great potential for precise tumor imaging diagnosis but has been minimally explored. Herein, we rationally design a DNA@Cu-MOF nanosystem containing copper metal–organic frameworks (Cu-MOF) and a DNAzyme-assisted signal amplification procedure for deregulated miRNA-related hypoxic tumor diagnosis. The nanoprobes comprising a signal strand block Cu-specific DNAzyme precursor and a substrate strand are assembled on the surface of the hypoxia-responsive Cu-MOF. Under TME characterized by hypoxia, the DNA@Cu-MOF nanosystem disassociates and accomplishes the release of abundant Cu2+, DNAzyme precursor, and substrate strand. Target aberrant miRNA displaces the signal strand to recover one fluorescence signal for detection. Importantly, it activates the Cu-specific DNAzyme amplification, which produces miRNA aberrant expression-dependent fluorescence signal for hypoxic tumor diagnosis. Both in vitro and in vivo experiments validate its good performance for tumor cell diagnosis. The hypoxia-driven and miRNA-binding-induced self-powered and temporal-spatial fluorescence imaging nanosystem not only provides a great tool for aberrant miRNA-related hypoxic tumor diagnosis but also is readily applied for the control and modulation of biological functions.
研究领域:
生物医学工程
·
分子生物学
·
纳米医学
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Yi Jin,Wei Yu,Wenkai Zhang,Chen Wang,Yao Liu,Wei-En Yuan,Yun Feng
Gene delivery for non-small-cell lung cancer treatment has been a challenge due to low nucleic acid binding ability, cell-wall barrier, and high cytotoxicity. Cationic polymers, such as the traditional “golden standard” polyethyleneimine (PEI) 25 kDa have emerged as a promising carrier for non-coding RNA delivery. However, the high cytotoxicity associated with its high molecular weight has limited its application in gene delivery. To address this limitation, herein, we designed a novel delivery system using fluorine-modified polyethyleneimine (PEI) 1.8 kDa for microRNA-942-5p-sponges non-coding RNA delivery. Compared to PEI 25 kDa, this novel gene delivery system demonstrated an approximately six-fold enhancement in endocytosis capability and maintain a higher cell viability . In vivo studies also showed good biosafety and anti-tumor effects, attribute to the positive charge of PEI and the hydrophobic and oleophobic properties of the fluorine-modified group. This study provides an effective gene delivery system for non-small-cell lung cancer treatment.
研究领域:
癌症治疗
·
基因递送
·
药学
·
生物医学工程
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PubMed
高影响因子
European Review for Medical and Pharmacological Sciences
·
2018
·
IF 2.387
X. Lv,C.-Y. Li,P. Han,X.-Y. Xu
OBJECTIVE: MicroRNAs are a class of small non-coding RNAs that be involved in the pathogenesis of non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the effects of miR-520a-3p in cell growth and metastasis.MATERIALS AND METHODS: The mimics and inhibitor of miR-520a-3p were used to identify the effects of miR-520a-3p on cell proliferation and apoptosis using methylthiazol tetrazolium (MTT) assay and flow-cytometric method, respectively. Transwell assay was used to evaluate the cell migration and invasion. The protein expression levels related PI3K/AKT/mTOR signaling pathways were measured by Western blot.RESULTS: The results showed that miR-520a-3p overexpression could significantly inhibit cell proliferation and induce apoptosis, suppress cell migration and invasion. MiR-520a-3p overexpression could markedly reduce the ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) compared with control. However, miR-520a-3p overexpression could increase caspase-3 expression compared with control group. After inhibited the expression of miR-520a-3p, the capacity of cell proliferation, migration and invasion were increased, cell apoptosis was inhibited compared with control group. The ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, MMP-2 and MMP-9 were increased compared with control group.CONCLUSIONS: Our study suggested that miR-520a-3p could suppress the NSCLC proliferation, migration and invasion through PI3K/AKT/mTOR signaling pathway.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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PubMed
高影响因子
NANO
·
2026
·
IF 1.3
Wei Wei,Chenjie Tao,Yingying Zhou,Yongbin Meng,Peining Yan
Background: Cholangiocarcinoma (CCA) is an aggressive malignancy with poor prognosis, underscoring the need for novel diagnostic and therapeutic strategies. MicroRNAs (miRNAs) hold therapeutic promise but face delivery challenges. This study aimed to develop folic acid (FA)-targeted superparamagnetic albumin nanoparticles for miRNA delivery (FA-SAN-miRNA) and evaluate their potential for theranostic applications in CCA. Method: FA-SAN-miRNA was synthesized and characterized for size, zeta potential, morphology, magnetic properties, encapsulation efficiency, and drug release. In vitro studies assessed cytotoxicity, cellular uptake, proliferation inhibition in CCA cells (RBE, HuCCT1), and MRI contrast efficacy. In vivo targeting and tracking capabilities were evaluated in a CCA xenograft mouse model. Results: The synthesized FA-SAN-miRNA nanoparticles were spherical, well-dispersed, and superparamagnetic, with a size of 236.25 ± 4.31 nm and a zeta potential of 30.73 ± 5.82 mV. They exhibited high miRNA encapsulation efficiency (88.12 ± 4.63%) and a pH-responsive sustained release profile. FA-SAN-miRNA demonstrated low cytotoxicity, enhanced cellular uptake, and significant inhibition of CCA cell proliferation compared to non-targeted controls. The nanoparticles served as effective T2 contrast agents for MRI. In vivo, FA-SAN-miRNA identifying tumor cells with capture efficiency correlating with tumor burden. Conclusion: The FA-SAN-miRNA platform successfully integrates targeted miRNA delivery, pH-responsive release, and MRI capability, demonstrating potential for identifying tumor cells and targeted delivery in CCA. This multifunctional nanoplatform offers a promising strategy for improving CCA management.
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高影响因子
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