American Journal of Translational Research
·
2021
·Vol. 13
·期 4
·2111-2126
·
IF 4.06
Chao Shi,Chongwen Shen,Ge Liu,Shaofeng Yang,Fenglin Ye,Jinjin Meng,Youmin Pan
Purpose To clarify the regulatory effect of Nuclear-enriched abundant transcript 1 (NEAT1) on abdominal aortic aneurysm (AAA) model rats and isolated endothelial progenitor cells (EPCs). Methods The AAA rat model was established by CaCl 2 stimulation, and overexpressed NEAT1 was injected into rats through tail vein. Abdominal aorta lesions and numbers of EPCs in tissues and peripheral blood were examined by hematoxylin-eosin, immunofluorescence and flow cytometry. The extracted EPCs were identified by microscopy, DiI-ac-LDL staining and flow cytometry. Effect of overexpressed/silencing NEAT1 on the viability, migration, tube formation and VEGF content of EPCs was investigated by MTT-, wound-healing, tube formation assays and ELISA, respectively. The expressions of NEAT1, miR-204-5p, Angiopoietin-1 (Ang-1)/ERK pathway were determined by qRT-PCR and Western blot as needed. The targeting relationships between NEAT1 and miR-204-5p, and miR-204-5p and Ang-1 were predicted on starBase, TargetScan and confirmed by dual-luciferase experiments. The mutual regulation effect was studied through rescue experiments. Results Overexpressed NEAT1 not only reduced inflammatory infiltration and increased the number of EPCs in abdominal aorta and peripheral blood, but also promoted the viability, migration, tube formation of EPCs, increased VEGF content and upregulated the expression of the Ang-1/ERK pathway in EPCs. However, silencing NEAT1 produced opposite results. NEAT1 targeting miR-204-5p inhibited the functional effects of miR-204-5p on of EPCs. Overexpressed/silencing Ang-1 partially reversed the effects of NEAT1 or miR-204-5p on the characteristics of EPCs. Conclusion NEAT1 competitively binds with miR-204-5p and up-regulates Ang-1 expression in EPCs to effectively improve the proliferation, migration and angiogenesis of EPCs.
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PubMed
高影响因子
Small
·
2018
·Vol. 14
·期 10
·1703858
·
IF 9.598
Keying Zhang,Lin Yang,Feng Lu,Xingcai Wu,Jun-Jie Zhu
Here, a sensitive and universal noncoding RNA (ncRNA) upconversion sensing nanoplatform is developed. Gold nanoparticles bearing one hairpin DNA (Hp) molecule are conjugated to the linker DNA modified NaYF 4 :Yb, Er@NaYF 4 upconversion nanoparticles by DNA hybridization, leading to quenching of the upconversion emission through fluorescence resonance energy transfer. A signal DNA (SDNA) sequence is designed to open Hp, recovering the upconversion emission. To achieve universality and high sensitivity of the nanoprobe, an exonuclease III (Exo III)-assisted cycling amplification strategy is introduced. A multifunctional hairpin DNA (mHp) containing ncRNA recognition sequence and SDNA sequence is designed to recognize ncRNA and trigger Exo III as a biocatalyst to stepwise disintegrate itself, releasing both ncRNA and SDNA. The released ncRNA can be reused to release more SDNA, which greatly improves the sensing sensitivity. By changing the recognition portion of mHp, various ncRNA can be detected. The sensitive detection of both homeobox (HOX) transcript antisense RNA segment and miR-21 is achieved with this novel strategy, even in human serum, indicating the universality and sensitivity of the proposed strategy. Additionally, the expression level of miR-21 in human breast cancer cell (MCF-7) lysate is successfully measured, suggesting its potential in clinical diagnosis.
研究领域:
生物技术
·
纳米技术
·
癌症诊断
·
分子生物学
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PubMed
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2020
·Vol. 10
·期 6
·874-883
·
IF 0.511
Zhang Li,Wei Shiyou,Xu Zhenkai,Sun Wen,Hang Lihua
Background: Cervical cancer is a type of malignancy with high incidence and high mortality in women all over the world. Recent findings revealed the role of sevoflurane in the inhibition of development of various cancer types. This study aimed to explore whether sevoflurane could
suppress cells proliferation and metastasis through adjusting miR-203 expression in cervical cancer. Methods: The effects of sevoflurane on HeLa cell viability was assessed using CCK-8 assay. miR-203 level in Hela cells was determined by qRT-PCR. In addition, cells apoptosis, migration
and invasion were evaluated using flow cytometry and transwell analysis respectively after sevoflurane treatment or miR-203 expression changes. Bioinformatics software (TargetScan) was used to predict the potential target genes for miR-203 and the prediction was validated using dual-luciferase
reporter system. Results: Sevoflurane effectively inhibited cell viability, metastasis and stimulated apoptosis in cervical cancer. miR-203 demonstrated a low expression in cervical cancer tissues and cells and sevoflurane significantly up-regulated miR-203 expression in cervical cancer
cells. Upregulation of miR-203 significantly suppressed cell growth and metastasis and induced apoptosis, while down-regulation of miR-203 presented the opposite effects in cervical cancer cells. In addition, the inhibitory effects of sevoflurane were eliminated by down-regulating miR-203
in cervical cancer cells. In addition, TPT1 was confirmed as a target gene for miR-203. Conclusion: Sevoflurane inhibited cervical cancer cells viability and metastasis through up-regulation of miR-203 expression by targeting TPT1.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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DOI
高影响因子
Journal of Functional Foods
·
2022
·
IF 5.223
Bo Jiang,Xinsheng Fu,Qichuan Zhang,Yunfei Du
Dioscin (DS) is a natural compound with inhibitory effects on multiple cancer types and we explored the mechanism driving the antagonizing effect of DS on osteosarcoma (OS). OS cell lines were treated with DS and microRNAs (miRs) responding to DS treatment were determined. Effects of DS on viability, apoptosis, metastasis, and miR-16-5p/HuR/Pim1 pathway activity were assessed. MiR-16-5p was inhibited before DS treatment to confirm its central role in anti-OS effects of DS. The conclusion derived from in vitro assays was verified with a mouse model. DS suppressed viability, invasion and migration, while induced apoptosis in OS cells. Moreover, the compound also induced the expression of miR-16-5p, contributing to the inhibition of HuR/Pim1 pathway. The inhibited expression of miR-16-5p counteracted the anti-OS function of DS, which was also validated in mice. Anti-OS effects of DS depended on the induction of miR-16-5p, making the compound a promising adjuvant agent for treating OS.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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高影响因子
Immunity Inflammation and Disease
·
2023
·Vol. 11
·期 2
·e730
·
IF 3.2
Min Liu,Shuang Liu,Fajiu Li,Chenghong Li,Shi Chen,Xiaoyan Gao,Xiaojiang Wang
Objective Asthma is a chronic respiratory disease with an increasing incidence every year. microRNAs (miRNAs) have been demonstrated to have implications for asthma. However, limited information is available regarding the effect of miR-124-3p on this disease. Therefore, this study aimed to explore the possible effects of miR-124-3p and S100A4 on inflammation and epithelial–mesenchymal transition (EMT) in asthma using mouse models. Method Ovalbumin was used to induce asthmatic mouse models. Lung injury in mouse models was assessed, and the bronchoalveolar lavage fluid of mice was collected to determine the number of eosinophilic granulocytes and assess inflammation. The expression levels of miR-124-3p, S100A4, E-cadherin, N-cadherin, Snail1, vimentin, and TGF-β1/Smad2 signaling pathway-related proteins were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. In vitro experiments, cells were transfected with miR-124-3p mimics or inhibitors to test the expression of S100A4 by RT-qPCR and western blot analysis, and the mutual binding of miR-124-3p and S100A4 was validated by dual-luciferase reporter gene assay. Results Overexpression of miR-124-3p or inhibition of S100A4 expression attenuated bronchial mucus secretion and collagenous fibers and suppressed inflammatory cell infiltration. Additionally, upon miR-124-3p overexpression or S100A4 suppression, eosinophilic granulocytes were decreased, interleukin-4 (IL-4) and IL-13 expression levels were reduced in the bronchoalveolar lavage fluid, serum total IgE level was reduced, and the TGF-β1/Smad2 signaling pathway was suppressed. Mechanically, a dual-luciferase reporter gene assay verified the binding relationship between miR-124-3p and S100A4. Conclusion miR-124-3p can negatively target S100A4 to attenuate inflammation in asthmatic mouse models by suppressing the EMT process and the TGF-β/smad2 signaling pathway.
研究领域:
免疫学
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分子生物学
·
呼吸医学
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DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2020
·
IF 4.486
Runxiao Lv,Lili Du,Fenghua Zhou,Xiangnan Yuan,Xueyong Liu,Lixin Zhang
Parkinson’s disease (PD) is the second most common neurodegenerative disorder mainly occurring in the elderly. MicroRNA-155-5p (miR-155-5p) plays a vital role in neurodegenerative disease and has been reported to be regulated by rosmarinic acid (RA). In our previous study, it was found that RA could improve motor function and alleviate inflammatory responses in a mice model of PD. This study aimed to investigate the role of miR-155-5p in RA-treated PD mice. The PD mice model was established by injecting mice with N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) and treated with RA or/and miR-155-5p agomir. The effects of miR-155-5p agomir on motor function, microglial activation, inflammation, apoptosis, and oxidative stress were analyzed by performing a behavioral test, ionized calcium-binding adapter molecule 1 staining, quantitative real-time PCR, Western blot, enzyme-linked immunosorbent assay, tyrosine hydroxylase (TH)-terminal dUTP nick end labeling double staining, TH-cleaved-caspase 3 double staining, and assessment of antioxidative parameters in RA-treated PD mice. The interaction between miR-155-5p and suppressor of cytokine signaling 1/nuclear factor erythroid 2-related factor 2 was validated using dual-luciferase reporter assay. MiR-155-5p up-regulation inhibited the alleviation of motor deficits caused by RA in PD mice, as evidenced by increasing descending time, decreasing limb movement score, increasing the time crossing the beam, and decreasing the times of front limb use. MiR-155-5p up-regulation could elevate microglial activation, inflammation, apoptosis, and oxidative stress in RA-treated PD mice. In conclusion, RA was able to alleviate PD by regulating miR-155-5p, suggesting that miR-155-5p could be used as a therapeutic target for PD treatment.
研究领域:
神经科学
·
药理学
·
分子生物学
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PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Lianjie Lin,Dongxu Wang,Suxuan Qu,Hong Zhao,Yan Lin
Introduction Ulcerative colitis (UC) is a chronic and inflammatory bowel disease. UC-associated colorectal cancer (UC-CRC) is one of the most severe complications of long-standing UC. In the present study, we explored the effects of miR-370-3p on UC-CRC in vivo and investigated its underlying mechanisms in vivo and in vitro.Methods Azoxymethane (AOM) and dextran sodium sulfate (DSS) were used to induce UC-CRC in C57BL/6 mice. AOM/DSS-induced mice were treated with 5×108 pfu miR-370-3p overexpressing-adenovirus via tail-vein injection every two weeks.Results We found that miR-370-3p significantly improved the body weights and survival rates and inhibited the tumorigenesis of UC-CRC in AOM/DSS mice. Mechanically, miR-370-3p inhibited AOM/DSS-induced inflammatory response by decreasing tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) through targeting toll-like receptor 4 (TLR4), as demonstrated by down-regulation of TLR4, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and phosphorylated epidermal growth factor receptor (pEGFR). miR-370-3p decreased the expression of tumor-associated proteins, including p53, β-catenin, and ki67 in AOM/DSS-treated mice. Additionally, miR-370-3p remarkably inhibited epithelial-mesenchymal transition (EMT) via increasing E-cadherin expression and reducing N-cadherin and Vimentin expression in vivo. Further studies showed that miR-370-3p repressed proliferation and EMT of colon cancer cells in vitro. Moreover, we proved that miR-370-3p decreased the expression of tumor-associated proteins and reversed EMT by regulating β-catenin in colon cancer cells.Conclusion Taken together, miR-370-3p alleviated UC-CRC by inhibiting the inflammatory response and EMT in mice, which suggested miR-370-3p as a novel potential target for UC-CRC therapy.
研究领域:
胃肠病学
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肿瘤学
·
分子生物学
·
免疫学
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PubMed
高影响因子
Analytical Cellular Pathology
·
2021
·
IF 2.916
Teng Zhang,Xiaomin Chen,Yueqing Qu,Yanbing Ding
Oxidative stress-induced neuronal damage is a main cause of ischemia/reperfusion injury. Curcumin (Cur), the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric), exhibits excellent antioxidant effects. Previous studies have indicated that miR-1287-5p was downregulated in patients with ischemic stroke. Additionally, we predicted that Lon Peptidase 2, Peroxisomal (LONP2), which is involved in oxidative stress regulation, is targeted by miR-1287-5p. The aim of the current study is to investigate the effect of Cur on ischemia/reperfusion damage and its underlying mechanism. To mimic ischemia/reperfusion damage environment, SH-SY5Y cells were subjected to oxygen-glucose-deprivation/reperfusion (OGD/R). OGD/R treatment downregulated miR-1287-5p and upregulated LONP2 in SH-SY5Y cells, but Cur alleviated OGD/R-induced oxidative damage and reversed the effect of OGD/R on the expression of miR-1287-5p and LONP2. Furthermore, we confirmed the interactive relationship between miR-1287-5p and LONP2 (negative regulation). We revealed that miR-1287-5p overexpression alleviated OGD/R-induced oxidative damage alleviation, similar to the effect of Cur. MiR-1287-5p inhibition accentuated OGD/R-induced oxidative damage in SH-SY5Y cells, which was reversed by Cur. The expression of LONP2 in OGD/R-treated SH-SY5Y cells was decreased by miR-1287-5p overexpression and increased by miR-1287-5p inhibition, and Cur counteracted the increase in LONP2 expression induced by miR-1287-5p inhibition. In conclusion, we suggest that Cur alleviates OGD/R-induced oxidative damage in SH-SY5Y cells by regulating the miR-1287-5p/LONP2 axis. The findings provide a theoretical basis for the clinical application of curcumin.
研究领域:
神经科学
·
分子生物学
·
药理学
·
细胞生物学
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DOI
PubMed
高影响因子
Biotechnology & Genetic Engineering Reviews
·
2023
·
IF 3.2
Lei Zhao,Houbin Zhang,Peiyou Ren,Xiangjun Sun
Triptolide (TP) is involved in the progression of liver cancer. However, the detailed molecular network regulated through TP is still unclear. Long non-coding RNA (LncRNA) SLC9A3 exerts roles in various pathological progresses. Nevertheless, whether SLC9A3 affects the sensitivity of liver cancer cells to TP have not been uncovered. The content of SLC9A3-AS1 and miR-449b-5p was estimated by utilizing quantitative real-time polymerase-chain reaction (qRT-PCR). Cell counting kit 8 (CCK-8) assay was introduced to assess cell viability. Additionally, cell viability as well as invasion was tested via transwell assay. The direct binding between miR-449b-5p and SLC9A3-AS1 or LDHA was confirmed through luciferase reporter gene assay. Moreover, glycolysis rate was tested by calculating the uptake of glucose in addition to the production of lactate in Huh7 cells. LncRNA SLC9A3-AS1 was up-regulated in liver cancer tissue samples and cells. Knockdown of SLC9A3-AS1 notably further inhibited viability, migration as well as invasion in Huh7 cells. MiR-449b-5p was the direct downstream miRNA of SLC9A3-AS1 and was down-regulated by SLC9A3-AS1 in Huh7 cells. In addition, miR-449b-5p was reduced in liver cancer tissues and cells. Overexpressed miR-449b-5p increased the sensitivity of Huh7 cells to TP remarkably. Moreover, miR-449b-5p negatively regulated LDHA expression in Huh7 cells. This work proved that SLC9A3-AS1 increased the sensitivity of liver cancer cells to TP by regulating glycolysis rate mediated via miR-449b-5p/LDHA axis. These findings implied that TP is likely to be a potent agent for treating patients diagnosed with liver cancer.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF GENE MEDICINE
·
2020
·Vol. 22
·期 9
·e3201
·
IF 3.258
Liping Ma,Yanjing Cao,Lin Zhang,Ketao Li,Laixing Yan,Yizhan Pan,Jianhua Zhu
Background Celastrol (Cel) has been corroborated as an anti-inflammatory and anti-apoptotic agent in multiple cell damage models. However, the protective effect of Cel in high glucose (HG)-induced cardiomyocyte injury is still unclear. The present study aimed to determine whether Cel can mitigate HG-stimulated cardiomyocyte injury via regulating the miR-345-5p/growth arrest-specific 6 (Gas6) signaling pathway. Methods Cardiomyocytes were exposed to normal glucose (NG; 5 mmol/l) or HG (30 mmol/l) and then administered with Cel. Cell counting kit-8 and flow cytometry assays were used to detect cell proliferative activity and apoptosis. mRNA and protein expression were analyzed using a quantitative reverse transcriptase-polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm and a luciferase reporter gene assay were used to determine whether Gas6 is a direct target of miR-345-5p. Results The present study confirmed the inhibitory effects of Cel in HG-induced inflammation in cardiomyocytes. Moreover, Cel exhibited the ability to antagonize HG-induced cardiomyocyte apoptosis and suppress the elevated Bax/Bcl-2 ratio elicited by HG stimulation. Intriguingly, Cel treatment revoked the HG-triggered repression of Gas6 protein expression, and Gas6 loss-of-function accelerated HG-induced cardiomyocyte apoptosis. HG-triggered up-regulation of miR-345-5p expression was depressed following Cel treatment. Importantly, we validated that Gas6 is a direct target of miR-345-5p. Transfection with miR-345-5p inhibitors restrained HG-induced release of pro-inflammatory cytokines and cell apoptosis. Conclusions The findings of the present study demonstrate that Cel administration antagonized HG-induced cardiomyocyte apoptosis and inflammation through up-regulating Gas6 expression by restraining miR-345-5p.
研究领域:
心脏病学
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分子生物学
·
药理学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2026
·
IF 10.4
Zhi Hu,Jiapeng Chen,Hengyong Xu,Xuyang Ji,Jiajun Zhu,Longge Guo,Xinqi Wang,Yiping Liu,Chaowu Yang,Chunlin Yu,Zengrong Zhang,Mohan Qiu,Yan Wang
Understanding the biochemical basis of chicken meat flavor is important for improving meat quality. An integrated metabolomic, lipidomic, and transcriptomic approach was applied to compare breast (BM) and leg meat (LM) of 120-day-old Tianfu broilers. Compared with BM, LM showed higher pH values, a 43.05% lower drip loss, and markedly higher intramuscular fat (IMF) content (6.217% vs. 1.954%), whereas BM contained more inosine monophosphate and exhibited greater shear force. GC–MS and lipidomics identified 147 volatile compounds and 1972 lipid species, respectively, with glycerophospholipids, particularly phosphatidylethanolamine and phosphatidylcholine, closely associated with flavor differences between muscles. Multi-omics factor analysis indicated circ_015424 as a key molecular feature correlated with lipid metabolism and flavor-related pathways. Functional assays further showed that circ_015424 enhanced lipid droplet accumulation in intramuscular adipocytes via the miR-196-1-3p/MOGAT1 axis. These results clarify lipid-related mechanisms underlying muscle-specific flavor formation in chicken.
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DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2026
·Vol. 24
·期 1
·492
·
IF 9.7
Li Ze,Ling Yimin,Xiao Wei,Li JiaZheng,Rong JiaHui,Zhang Zewen,Wei Yan,Huo Zhongchao,Li Dong
Background Scutellarin (SCU) is a natural flavonoid compound exhibiting anti-tumor activity. This study aimed to elucidate the molecular mechanism underlying SCU’s therapeutic effects in liver cancer. Methods An integrated approach combining network pharmacology and transcriptomic analysis was employed to identify SCU-related targets, followed by the identification of core targets through protein–protein interaction (PPI) network construction and topological analysis using MCC and MCODE algorithms. A circular RNA (circRNA)-mediated competing endogenous RNA (ceRNA) regulatory network was constructed by integrating data from databases including miRWALK and circBANK with whole-transcriptome sequencing. Molecular interactions were experimentally validated using Western blotting, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP). In Huh7 and HepG2 cells, overexpression and knockdown models of key RNAs were established to evaluate their functional roles, with cell proliferation, cell cycle distribution, and apoptosis assessed via CCK-8, colony formation, and flow cytometry assays. To investigate in vivo anti-tumor efficacy and associated mechanisms, a subcutaneous xenograft tumor model was established in nude mice. Results Integrated network pharmacology and transcriptomic analysis identified 11 core genes significantly enriched in the estrogen signaling pathway, among which ESR1 was validated as a key target. SCU downregulated ESR1 expression in a dose-dependent manner. Mechanistically, SCU upregulated miR-2682-5p while downregulating circSRBD1. Dual-luciferase reporter assays confirmed that miR-2682-5p directly binds to the 3′UTRs of both circSRBD1 and ESR1, supporting the existence of a circSRBD1/miR-2682-5p/ESR1 ceRNA regulatory axis. Functional studies demonstrated that overexpression of circSRBD1 attenuated SCU-induced cell cycle arrest, apoptosis, and suppression of proliferation, whereas silencing circSRBD1 enhanced these effects. Furthermore, SCU and fulvestrant exhibited synergistic anti-tumor activity both in vitro and in vivo. Conclusion This study identifies a novel circSRBD1/miR-2682-5p/ESR1 ceRNA regulatory axis that plays a critical role in mediating SCU’s inhibitory effects on liver cancer progression, highlighting the potential therapeutic value of combining SCU with fulvestrant. Clinical trial number Not applicable.
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PubMed
高影响因子
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