Cancer Cell International
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2021
·Vol. 21
·期 1
·1-13
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IF 5.722
Lei Jie,Chen Peng,Zhang Feng,Zhang Na,Zhu Jianfei,Wang Xiaoping,Jiang Tao
Background Exosomes are known to transmit microRNAs (miRNAs) to affect cancer progression, while the role of M2 macrophages-derived exosomes (M2 exosomes) conveying miR-501-3p in lung cancer (LC) remains unknown. We aim to explore the role of exosomal miR-501-3p in LC development via targeting WD repeat domain 82 (WDR82). Methods Lung cancer tissue and normal tissue specimens were collected, in which tumor-associated macrophages (TAM) were measured by immunohistochemistry. M2 macrophages were induced and treated with altered miR-501-3p, and then the exosomes were extracted and identified. MiR-501-3p and WDR82 expression in LC tissues and cell liens was determined. The predictive role of miR-501-3p in prognosis of LC patients was assessed, and the proliferation, colony formation ability, invasion, migration and apoptosis of the LC cells were determined. Targeting relationship between miR-501-3p and WDR82 was confirmed. Results TAM level was elevated in lung cancer tissues. MiR-501-3p was upregulated while WDR82 was downregulated in LC tissues and cell lines, and the M2 exosomes further upregulated miR-501-3p. M2 exosomes and exosomal miR-501-3p promoted LC cell growth. MiR-501-3p inhibition reversed the effect of M2 exosomes on LC cells. WDR82 was confirmed as a target gene of miR-501-3p. Conclusion M2 macrophages-derived exosomal miR-501-3p promotes the progression of LC via downregulating WDR82.
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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高影响因子
Pharmaceutics
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2026
·Vol. 18
·期 3
·363
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IF 6.9
Meitong Liu,Kai Wang,Can Zeng,Yijiang Jia,Jiaqi Wang,Ayijiang Taledaohan,Yuji Wang,Xiaobing Guan
Purpose:Due to the lack of effective local therapeutic strategies for oral squamous cell carcinoma (OSCC), this study aimed to develop a novel gelatin/lignin hydrogel loaded with mesenchymal stem cell (MSC)-derived exosomes enriched in microRNA-185 (miR-185 EV) for intraoral delivery, followed by systematic evaluation of its therapeutic efficacy and underlying molecular mechanisms.Materials and Methods:The gelatin/lignin hydrogel was prepared and subsequently loaded with miR-185 EV. The physicochemical properties of the hydrogel, including microstructure, swelling behavior, chemical composition, and rheological characteristics, were systematically evaluated. Next, the stability, viscosity, biocompatibility, and exosome release kinetics of the hydrogel were further assessed. A 4-nitroquinoline-1-oxide (4NQO)-induced mouse tongue carcinogenesis model was established to assess the in vivo antitumor activity of the hydrogel via intraoral administration. Moreover, a proteomic analysis was conducted to investigate the molecular mechanisms of miR-185 EV on OSCC.Results:The miR-185 EV-loaded gelatin/lignin hydrogel exhibited favorable physicochemical properties, stability, and biocompatibility while prolonging the tissue retention time of miR-185 EV. In vivo antitumor efficacy experiments showed that the miR-185 EV-loaded hydrogel significantly inhibited tumor occurrence and alleviated epithelial dysplasia. Immunohistochemical analyses revealed significant suppression of tumor proliferation and epithelial–mesenchymal transition (EMT) of the hydrogel. Proteomic analysis indicated that miR-185 EV suppressed OSCC progression by downregulating interleukin-1β (IL-1β), consequently inhibiting the NF-κB signaling pathway.Conclusion:The findings demonstrate the successful development of the miR-185 EV-loaded gelatin/lignin hydrogel that represents an effective nanomedicine platform for intraoral drug delivery, providing a promising strategy for the clinical treatment of OSCC.
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MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 9
·1-9
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IF 5.479
Chen Dongli,Zhang Meng,Zhou Fenyue,Hai Hong,Li Jianping
An electrochemiluminescent (ECL) biosensor is described for the determination of the breast cancer biomarker microRNA. The method is based on the amplification via target cyclic regeneration through a system of hairpin DNA probes, primers, and Klenow fragment of DNA polymerases combined with CdTe quantum dots (QDs) and gold nanoparticles. The assay is performed by exploiting the luminescence properties of CdTe-QDs and K 2 S 2 O 8 as a co-reactive agent to increase the ECL signal. It was successfully applied to ECL-based detection of a 20-mer microRNA. The sensor has a linear response in the 0.1 fM to 0.2 pM microRNA concentration range and a detection limit as low as 33 aM. The assay has been applied to the determination of microRNA spiked in serum samples, and recoveries ranged from 94.4 to 100.5%.
A novel electroluminescence biosensor based on the amplification of target cyclic regeneration is described. It is achieved by using a system of hairpin DNA probes, primers, and Klenow fragment of DNA polymerases combined with CdTe QDs and Au NPs, and was successfully applied to microRNA detection.
研究领域:
生物传感器
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癌症研究
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纳米技术
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分子诊断
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电化学
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SENSORS AND ACTUATORS B-CHEMICAL
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2020
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IF 7.1
Sze Shin Low,Yixin Pan,Daizong Ji,Yaru Li,Yanli Lu,Yan He,Qingmei Chen,Qingjun Liu
Circulating microRNAs (miRNAs) are effective cancer biomarkers that are highly stable in body fluids enabling noninvasive detection. Portable, low-cost and efficient biosensing systems is crucial for early on-site diagnosis, especially in resource-limited settings. Present work deals with the development of a smartphone-based biosensing system for electrochemical detection of circulating microRNA-21 (miR-21) biomarker in saliva as a proof-of-concept. The smartphone-based biosensing system composed of a disposable screen-printed biosensor modified with reduced graphene oxide/gold (rGO/Au) composite, a circuit board for detection and a Bluetooth-enabled smartphone equipped with specially designed Android application. The hybridization between miR-21 target and ssDNA probe on the rGO/Au-modified electrode resulted in the decrease in peak current with increase in miR-21 target concentration. The smartphone-based biosensing system showed comparable performance with commercial electrochemical workstation, for miR-21 detection in the concentration range of 1 × 10 −4 M to 1 × 10 -12 M with correlation coefficient (r 2 ) of 0.99. In addition to good selectivity in discriminating mismatched and non-target sequences, the biosensing system also showed acceptable recovery rate ranging from 96.2%–107.2 % in spiked artificial saliva. The smartphone-based biosensing system is envisioned to be able to realize rapid and highly sensitive detection of circulating miRNA biomarker in body fluid for point-of-care testing in remote areas.
研究领域:
生物医学工程
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生物传感器
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即时诊断
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癌症生物标志物
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电化学
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2023
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IF 8.4
Weidong Qin,Junhua Wang,Zhanqiu Tang,Hongyuan Tian,Zhenglong Wu
Quick and efficient immobilization of DNAs on gold nanoclusters (AuNCs) has a substantial impact on nanoscale applications relative to molecular recognition and patterned assembly. We found that in the presence of tris(2-carboxyethyl)phosphine (TCEP), chemisorption of thiolated DNA on the AuNC surface could be accomplished within 1.5 h, which was dramatically shorter than the incubation time needed in the conventional thiolate exchange reactions. Based on this observation, a core-shell-satellite nanocomposite consisting of magnetic nanoparticle , silica coating, and AuNCs (Fe 3 O 4 NPs@SiO 2 @AuNCs) was fabricated, on which a fluorescent hairpin probe was anchored with the assistance of TCEP. Integrated with duplex-specific nuclease (DSN)-assisted target recycling strategy, the sensing platform could simultaneously detect microRNA-21 and microRNA-141 with detection limits of 0.020 and 0.017 pM, respectively. The feasibility of the developed immobilization approach might significantly advance the use of DNAs and AuNCs in analytical sciences and clinical research.
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ADVANCED FUNCTIONAL MATERIALS
·
2018
·Vol. 28
·期 28
·1801118
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IF 13.325
Hai-Jun Liu,Xin Luan,Hai-Yi Feng,Xiao Dong,Si-Cong Yang,Zhong-Jian Chen,Qin-Yi Cai,Qin Lu,Yunpeng Zhang,Peng Sun,Mei Zhao,Hong-Zhuan Chen,Jonathan F. Lovell,Chao Fang
Mesoporous silica nanoparticles (MSN) can load and deliver potentially synergistic anticancer agents such as small molecule cytotoxics (like doxorubicin, DOX) and nucleic acids (like microRNA, miRNA). However, these cargos have different underlying chemical properties so overcoming respective intracellular delivery barriers is a key consideration. Strategies to deliver DOX from MSN frequently employ pH-driven mechanisms that are restricted to the acidic environment of lysosomes. Conversely, strategies to deliver miRNA make use of approaches that deliberately compromise lysosomal membrane integrity to enable cytosolic delivery of the payload. To reconcile these two needs (lysosomal delivery of DOX and intracellular delivery of miRNA), a new methodology by “weaving” polyethylenimine on the MSN surface through disulfide bonds to achieve superior delivery of chemotherapy (DOX) and miRNA therapy (using miRNA-145) is developed. Furthermore, an active targeting strategy based on a peptide ligand with affinity to glucose-regulated protein 78 (GRP78), a cell surface protein overexpressed in colorectal carcinoma, is developed. The active targeting approach results in enhanced synergistic antitumor effect both in vitro and in vivo in an orthotopic murine model of colorectal cancer. Taken together, this work demonstrates the capability and advantages of “smart” MSN delivery systems to deliver anticancer cargo appropriately to targeted cancer cells.
研究领域:
癌症研究
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纳米技术
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药学科学
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分子生物学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2018
·Vol. 19
·期 2
·447
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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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PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2016
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IF 4.712
Kai Shi,Baoting Dou,Jianmei Yang,Ruo Yuan,Yun Xiang
The monitoring of microRNA (miRNA) expression levels is of great importance in cancer diagnosis. In the present work, based on two cascaded toehold-mediated strand displacement reactions (TSDRs), we have developed a label- and enzyme-free target recycling signal amplification approach for sensitive electronic detection of miRNA-21 from human breast cancer cells. The junction probes containing the locked G-quadruplex forming sequences are self-assembled on the senor surface. The presence of the target miRNA-21 initiates the first TSDR and results in the disassembly of the junction probes and the release of the active G-quadruplex forming sequences. Subsequently, the DNA fuel strand triggers the second TSDR and leads to cyclic reuse of the target miRNA-21. The cascaded TSDRs thus generate many active G-quadruplex forming sequences on the sensor surface, which associate with hemin to produce significantly amplified current response for sensitive detection of miRNA-21 at 1.15 fM. The sensor is also selective and can be employed to monitor miRNA-21 from human breast cancer cells.
研究领域:
生物化学
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分子生物学
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癌症诊断
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纳米技术
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电化学生物传感器
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Shengnan Huang,Chengzhi Song,Jinxin Miao,Xiali Zhu,Yongyan Jia,Yafei Liu,Dongjun Fu,Benyi Li,Mingsan Miao,Shaofeng Duan,Zhenzhong Zhang,Yurong Hu
Dysregulation of microRNAs (miRNAs) expression is closely related to cancers and managing miRNA expression holds great promise for cancer therapy. However, their wide clinical application has been hampered by their poor stability, short half-life and non-specific biodistribution in vivo . Herein, a novel biomimetic platform designated as RHAuNCs-miRNA for improved miRNA delivery was prepared through wrapping miRNA-loaded functionalized Au nanocages (AuNCs) with red blood cell (RBC) membrane. RHAuNCs-miRNA not only successfully loaded miRNAs but also effectively protected them from enzymatic degradation. With good stability, RHAuNCs-miRNA had the characteristics of photothermal conversion and sustained release. Cellular uptake of RHAuNCs-miRNA by SMMC-7721 cells was in a time-dependent manner via clathrin- and caveolin-mediated endocytosis. The uptake of RHAuNCs-miRNAs was affected by cell types and improved by mild near infrared (NIR) laser irradiation. More importantly, RHAuNCs-miRNA exhibited a prolonged circulation time without the occurrence of accelerated blood clearance (ABC) in vivo, resulting in efficient delivery to tumor tissues. This study may demonstrate the great potential of RHAuNCs-miRNA for improved miRNAs delivery.
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高影响因子
Current Medical Science
·
2023
·Vol. 43
·期 2
·223-231
·
IF 2.4
Zhang Qing,Pan Rong-rong,Wu Yu-tao,Wei Yu-miao
Objective Vascular smooth muscle cell (VSMC) differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension, atherosclerosis, and restenosis. MicroRNA-146a (miR-146a) has been proven to be involved in cell proliferation, migration, and tumor metabolism. However, little is known about the functional role of miR-146a in VSMC differentiation from embryonic stem cells (ESCs). This study aimed to determine the role of miR-146a in VSMC differentiation from ESCs. Methods Mouse ESCs were differentiated into VSMCs, and the cell extracts were analyzed by Western blotting and RT-qPCR. In addition, luciferase reporter assays using ESCs transfected with miR-146a/mimic and plasmids were performed. Finally, C57BL/6J female mice were injected with mimic or miR-146a-overexpressing ESCs, and immunohistochemistry, Western blotting, and RT-qPCR assays were carried out on tissue samples from these mice. Results miR-146a was significantly upregulated during VSMC differentiation, accompanied with the VSMC-specific marker genes smooth muscle-alpha-actin (SMαA), smooth muscle 22 (SM22), smooth muscle myosin heavy chain (SMMHC), and h1-calponin. Furthermore, overexpression of miR-146a enhanced the differentiation process in vitro and in vivo . Concurrently, the expression of Kruppel-like factor 4 (KLF4), predicted as one of the top targets of miR-146a, was sharply decreased in miR-146a-overexpressing ESCs. Importantly, inhibiting KLF4 expression enhanced the VSMC-specific gene expression induced by miR-146a overexpression in differentiating ESCs. In addition, miR-146a upregulated the mRNA expression levels and transcriptional activity of VSMC differentiation-related transcription factors, including serum response factor (SRF) and myocyte enhancer factor 2c (MEF-2c). Conclusion Our data support that miR-146a promotes ESC-VSMC differentiation through regulating KLF4 and modulating the transcription factor activity of VSMCs.
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Bioengineered
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2021
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IF 3.269
Shanzhi Wan,Zhimin Liu,Yang Chen,Zhitao Mai,Mingming Jiang,Qingguo Di,Baohua Sun
MicroRNA (miR)-140-3p has been proved to repress lung adenocarcinoma (LUAD), and our study aims to further evaluate the mechanism. Bioinformatic analyses were performed. The viability, proliferation, migration, invasion and angiogenesis of transfected LUAD cells were all determined via Cell Counting Kit-8, colony formation, Scratch, Transwell, and tube formation assays. The targeting relationship between miR-140-3p and thymidylate synthetase (TYMS) was confirmed by dual-luciferase reporter assay. Relative expressions of miR-140-3p, TYMS, epithelial-to-mesenchymal transition- (E-cadherin, N-cadherin, vimentin), angiogenesis- (vascular endothelial growth factor (VEGF)), and apoptosis-related factors (cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax)) were quantified by quantitative real-time polymerase chain reaction or Western blot. TYMS was high-expressed yet miR-140-3p was low-expressed in LUAD cells. Upregulation of miR-140-3p inhibited TYMS expression, viability, colony formation, migration, invasion, and tube length within LUAD cells, while downregulation of miR-140-3p did oppositely. Silenced TYMS, the downstream target gene of miR-140-3p, reversed the effects of miR-140-3p downregulation on TYMS expression, cell viability, colony formation, migration, invasion, and tube length as well as the metastasis-, apoptosis- and angiogenesis-related proteins in LUAD cells. Upregulation of miR-140-3p inhibited the proliferation, migration, invasion and angiogenesis of LUAD cells via targeting TYMS.
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PubMed
高影响因子
Bioengineered
·
2021
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IF 3.269
Bo Li,Xianyi Liu,Guogang Wu,Jiawen Liu,Shouliang Cai,Fuxin Wang,Chunyu Yang,Jisheng Liu
Colorectal cancer (CRC) is a global public health issue with increasing prevalence. MicroRNA-934 (miR-934) is a kind of non-coding RNA involved in the regulation of diverse cancers. Though previous researches have revealed part of association between miR-934 and CRC, the role of miR-934 in CRC pathogenesis has not been completely explored yet. In this study, we aim to investigate the effect of miR-934 on cell proliferation, migration, invasion and angiogenesis in CRC. Accordingly, miR-934 was found to be over-expressed in SW480 and HCT116 cells, two typical CRC cell lines. Meanwhile, miR-934 knockdown significantly inhibited cell proliferation and induced cell cycle arrest in SW480 and HCT116 cells. It was further validated that miR-934 knockdown displayed an inhibitory effect on cell migration and invasion in SW480 and HCT116 cells. Additionally, miR-934 deficiency markedly decreased VEGF expression in SW480 and HCT116 cells and suppressed capability of CRC cells to promote tube formation in vascular endothelial cells, which suggests the pro-angiogenesis role of miR-934 in vitro. Dual luciferase reporter assay further showed that miR-934 directly bound to B-cell translocation gene 2 (BTG2). BTG2 knockdown reversed the inhibitory effect of miR-934 silencing on cell proliferation, migration, invasion, and angiogenesis in SW480 and HCT116 cells. In summary, this study suggests that miR-934 facilitates CRC progression by targeting BTG2, and further highlights the role of miR-934 in pathogenesis of CRC.
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