MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2020
·
IF 3.871
Ziwen Wei,Xiaoli Qin,Xiaojie Kang,Haixia Zhou,Shaodan Wang,Dong Wei
Background MiR-142-3p has been shown to be suppressed in obese patients , while the underlying regulatory mechanism is unclear. Methods Body shape indexes as well as peripheral blood for biochemical parameter analysis were obtained from obese and healthy subjects. When 3T3-L1 cells were induced to differentiate, miR-142-3p expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of miR-142-3p on triglyceride (TG) and adipogenic differentiation-related genes during the adipogenic differentiation of 3T3-L1 cells were detected by transfection, Oil Red O staining, and Western blot . The targeting relationship between miR-142-3p and Krueppel-like transcription factor 9 (KLF9) was verified by TargetScan and dual-luciferase experiment. The specific regulatory effects of miR-142-3p on cell adipogenic differentiation and autophagy were analyzed by rescue experiments. In vivo experiments further validated the results of in vitro experiments through obese mouse models. Results Obesity-marked biochemical indicators increased whereas high density lipoprotein and miR-142-3p decreased in obese patients. The content of miR-142-3p gradually decreased with cell lipid differentiation. Overexpression of miR-142-3p reduced TG deposition in cells by down-regulating lipid formation and fatty acid synthesis genes and up-regulating fatty acid oxidation genes. KLF9 targeting miR-142-3p was suppressed by miR-142-3p. KLF9 overexpression partially reversed the inhibitory effect of miR-142-3p mimic on adipogenic differentiation and the expressions of autophagy related-genes in 3T3-L1 cells. MiR-142-3p overexpression also inhibited fat cell differentiation and autophagy in obese mice . Conclusion Overexpressed miR-142-3p inhibited adipogenic differentiation and autophagy through targeting KLF9.
研究领域:
分子生物学
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细胞生物学
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内分泌学
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DOI
PubMed
高影响因子
Cellular Reprogramming
·
2018
·Vol. 20
·期 2
·99-106
·
IF 1.43
Mengya Zhao,Lin Li,Jundong Zhou,Xueyuan Cui,Qingmei Tian,Yaqing Jin,Yimin Zhu
Cancer stem cells (CSCs) are responsible for cancer initiating, recurrence, and drug resistance. Discovery of novel biomarkers for CSCs is helpful for early diagnosis and prognosis. Lung cancer stem cells (LCSCs) were closely related to the occurrence and development of lung cancer. In our study, the important role of miR-2861 in maintaining the stemness of LCSCs was investigated. The LCSC differentiation model was established through introducing serum into the medium of H460 spheres. miR-2861 expression was significantly higher in LCSCs no matter compared to the differentiation cells or normal cells. HDAC5 expression was positively correlated with miR-2861 in LCSCs, and knockdown of miR-2861 decreased the expression of HDAC5, which implied that HDAC5 may be involved in the differentiation of LCSCs mediated by miR-2861. The role of HDAC5 in the regulation of LCSC differentiation was further verified by the inhibitory effect of LMK-235 on the phosphorylation of ERK1/2, which was recognized as the regulator of CSC differentiation. Our study provided a better understanding of miR-2861 and HDAC5 axis in maintaining the stemness of LCSCs and laid a foundation for molecular targeted therapy.
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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DOI
PubMed
高影响因子
Human Cell
·
2025
·Vol. 38
·期 4
·1-13
·
IF 3.1
Lian Hongyu,Yu Miao,Li Qi,Xiao Jiayi,Tang Xin,Zhang Bin,Liu Dongxue,Xu Yongliang,Dong Mo,Li Zitao,Yao Lihong,Li Caijuan
Hypoxia is a critical mechanism within the microenvironment of tumors. Exosomes, serve as conduits for intercellular communication and transport the biomolecule miRNA by facilitating intercellular signal exchange, which partially regulate cancer metastasis. Our research investigated whether the role of hypoxic breast cancer cell-derived exosomal miR-143-3p in cancer progression. Real-time PCR explored miR-143-3p expression in hypoxia breast cancer cell-derived exosomes. Co-culturing of breast cancer with hypoxia exosome-primed M0 macrophages, transwell detected the invasiveness of breast cancer cells. Western blot showed the effect of hypoxia exosomes on the levels of M2 makers in macrophages and the epithelial-mesenchymal transition (EMT) indicators in breast cancer cells. Bioinformatics prediction and dual luciferase reporter assay determined the interaction between miR-143-3p and RICTOR. We found that exosomal miR-143-3p expression was downregulated in hypoxic conditions. Hypoxia breast cancer cell-derived exosomal miR-143-3p negatively correlated with the presentation of the M2 macrophage marker CD206 and regulated the levels of Arg-1, CD206 and CD163 mRNA levels. In addition, hypoxia exosome-mediated polarization of M2 macrophages promotes breast cancer cell migration and invasion. Mechanistically, miR-143-3p acted antagonistically with RICTOR, thereby suppressing macrophage M2 polarization. In summary, our study reveals that the hypoxia downregulates the exosomal miR-143-3p derived from breast cancer cells to increase macrophage RICTOR expression, thereby promoting M2 macrophage polarization to enhance breast cancer cell invasiveness, suggesting that miR-143-3p may be a candidate molecule for microRNA alternative therapy in breast cancer.
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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DOI
PubMed
高影响因子
Frontiers in Physiology
·
2021
·
IF 4.566
Wangzhou Kaixin,Lai Zhiying,Lu Zishao,Fu Wanren,Liu Cheng,Liang Zhengeng,Tan Yi,Li Conghui,Hao Chunbo
Human periodontal ligament cells (hPDLCs) play a vital role in cell regeneration and tissue repair with multi-directional differentiation potential. microRNAs (miRs) are implicated in the osteogenesis of hPDLCs. This study explored the mechanism of miR-143-3p in osteogenesis of hPDLCs. Osteogenic differentiation of isolated hPDLCs was induced. KLF5 expression during osteogenic differentiation of hPDLCs was detected and then silenced in hPDLCs. Binding relationship between KLF5 and miR-143-3p was predicted and verified. hPDLCs were treated with miR-143-3p mimic or overexpressing KLF5, and then osteogenic specific markers and mineralized nodules were measured. The key factors of the Wnt/β-catenin pathway during osteogenesis of hPDLCs were measured. KLF5 expression was upregulated during osteogenesis of hPDLCs. KLF5 silencing or miR-143-3p mimic reduced osteogenic specific markers and mineralized nodules. Overexpression of KLF5 could reverse the inhibitory effect of miR-143-3p on osteogenic differentiation. miR-143-3p mimic and KLF5 silencing inactivated the Wnt/β-catenin pathway. Activation of the Wnt/β-catenin pathway reversed the repression effect of miR-143-3p mimic on osteogenesis of hPDLCs. In conclusion, miR-143-3p inhibited osteogenic differentiation of hPDLCs by targeting KLF5 and inactivating the Wnt/β-catenin pathway.
研究领域:
牙科学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Wenjing Pu,Xuesheng Chu,Shiwen Xu,Xueyan Dai,Li Xiao,Ting Cui,Bingyan Huang,Guoliang Hu,Caiying Zhang
Molybdenum (Mo) is an essential nutrient in living organisms. Although numerous researchers have noticed the health damage caused by excessive Mo, the underlying mechanism of excessive Mo-induced nephrotoxicity remains poorly understood. A gene crosstalk called competitive endogenous RNAs (ceRNAs) can interpret many regulatory mechanisms molecularly. But there are few researches have tried to explain the damage mechanism of excess Mo to organisms through ceRNAs network. To clarify this, the study explored the changes in lncRNAs and miRNAs expression profiles in the kidney of ducks exposed to excess Mo for 16 weeks. The sequencing results showed that Mo exposure caused differential expression of 144 lncRNAs and 14 miRNAs. The occurrence of inflammation through the JAK/STAT axis was observed and the lncRNA-00072124/miR-308/OSMR axis was verified by a double luciferase reporter assay. Overexpression of miR-308 and RNA interference of OSMR reduced Mo-induced inflammatory factors, while miR-308 knockdown showed the opposite effect. Simultaneously, lncRNA-00072124 affected OSMR function as a ceRNA. Taken together, these results concluded that Mo exposure activated the JAK/STAT axis and induced inflammation mediated by the lncRNA-00072124/miR-308/OSMR crosstalk. The results might provide new views for revealing the toxic effects of excess Mo in duck kidneys.
研究领域:
毒理学
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分子生物学
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动物科学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Tong Liu,Siqing Fan,Pengfei Meng,Mingxia Ma,Yanxin Wang,Jiaojiao Han,Yufei Wu,Xiao Li,Xiurong Su,Chenyang Lu
Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3′-untranslated regions of gene pik3ca, inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.
研究领域:
微生物学
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药理学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Lin Peng,Shasha Chen,Hongjin Lin,Chunyan Wan,Xiang Li,Shiwen Xu,Shu Li
Bisphenol A (BPA) is an endocrine disruptor. Excessive BPA intake can damage the structure and function of the respiratory tract. Dietary selenium (Se) deficiency may also cause immune tissue damage. To investigate the potential mechanism of BPA on tracheal damage in selenium-deficient chickens and the role of microRNAs (miRNAs) in this process, we established in vitro and in vivo Se deficiency and BPA exposure models and screened out miR-155 for follow-up experiments. We further predicted and confirmed the targeting relationship between miR-155 and TRAF3 using TargetScan and dual luciferase assays and found that miR-155 was highly expressed and caused inflammatory damage. Further studies showed that BPA exposure increased airway oxidative stress, activated the NF-κB pathway, and caused inflammation and immune damage in selenium-deficient chickens, but down-regulating miR-155 and NAC treatment could reverse this phenomenon. This suggested that these pathways are regulated by the miR-155/TRAF3/ROS axis. In conclusion, BPA exposure aggravates airway inflammation in selenium-deficient chickens by regulating miR-155/TRAF3/ROS. This study revealed the mechanism of BPA exposure combined with Se deficiency in tracheal inflammatory injury in chickens and enriched the theoretical basis of BPA injury in poultry.
研究领域:
毒理学
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免疫学
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分子生物学
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兽医学
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PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 19
·期 1
·375-383
·
IF 1.448
Xiaowei Shen,Jiaqi Lei,Lei Du
The limited efficacy of chemotherapy with Taxol (TAX) and cisplatin (DDP) in triple‑negative breast cancer (TNBC) has prompted the investigation of combined therapies. Previous studies demonstrated that microRNA (miR)‑31‑5p is involved in various biological processes. In the present study, it was hypothesized that the overexpression of miR‑31‑5p may enhance the efficacy of chemotherapy. The expression levels of miR‑31‑5p in the TNBC cell lines MDA‑MB‑231 and MDA‑MB‑468 were measured using reverse transcription‑quantitative PCR following transfection with miR‑31‑5p mimic or inhibitor. A Cell Counting Kit‑8 and flow cytometry assays suggested that the overexpression of miR‑31‑5p inhibited cell proliferation and promoted apoptosis, and these effects were reversed by transfecting a miR‑31‑5p inhibitor into MDA‑MB‑231 and MDA‑MB‑468 cells. Furthermore, the overexpression of miR‑31‑5p increased the sensitivity of cells to chemotherapy, which exhibited an increase in apoptosis and in the expression level of Bax, and a decrease in the expression level of Bcl‑2. Chemotherapy resistance induced by miR‑31‑5p inhibitor could be reversed by inhibiting the AKT signaling pathway in MDA‑MB‑231 and MDA‑MB‑468 cells. In conclusion, the present preclinical results indicated that targeting miR‑31‑5p may enhance the efficacy of TAX‑ and DDP‑mediated chemotherapy in TNBC.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2023
·Vol. 51
·期 5
·1-16
·
IF 5.4
Sheng Huan,Sumin Sun,Shilian Song,Jin Dai,Guining Zhu,Yanling Zhong,Yihao Ji,Shizhong Zheng,Guoping Yin
Liver fibrosis is an early pathological feature of hepatic diseases. Hepatic stellate cell (HSC) activation and disordered proliferation are associated with liver fibrosis. The present study identified significant differences in the expression levels of microRNA (miRNA/miR)‑29b‑3p in clinical samples and multiple miRNA databases. Subsequently, the specific antifibrotic mechanism of miR‑29b‑3p was further elucidated. Reverse transcription‑quantitative PCR, western blot, ELISA and immunofluorescence were used to detect the expression levels of target genes and proteins. Oil red O, Nile red and trypan blue staining were used to evaluate HSC activation and cell viability. A luciferase assay was used to detect the relationship between miR‑29b‑3p and VEGFA. Adhesion, wound healing, apoptosis double staining and JC‑1 assays were used to detect the effects of VEGFR1 and VEGFR2 knockdown on HSCs. Immunoprecipitation and fluorescence colocalization were used to identify interactions between the proteins. Furthermore, a rat fibrosis model was constructed to investigate the effects of dihydroartemisinin (DHA) and miR‑29b‑3p in vivo and in vitro. The results indicated that miR‑29b‑3p both inhibited the activation of HSCs and limited the proliferation of activated HSCs via lipid droplet recovery and VEGF pathway regulation. VEGFA was identified as a direct target of miR‑29b‑3p, and knockdown of VEGFA induced cell apoptosis and autophagy. Notably, VEGFR1 and VEGFR2 knockdown both promoted apoptosis; however, VEGFR1 knockdown inhibited autophagy, whereas VEGFR2 knockdown induced autophagy. Furthermore, it was revealed that VEGFR2 regulated autophagy by mediating the PI3K/AKT/mTOR/ULK1 pathway. VEGFR2 knockdown also led to ubiquitination of heat shock protein 60, ultimately inducing mitochondrial apoptosis. Finally, DHA was identified as a natural agonist of miR‑29‑3p that effectively prevented liver fibrosis in vivo and in vitro. Overall, the present study determined the molecular mechanism by which DHA inhibited HSC activation and prevented liver fibrosis.
研究领域:
分子生物学
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药理学
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肝病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Therapy-Nucleic Acids
·
2020
·
IF 7.032
Yihao Liu,Jie Wang,Xiaomin Zhou,Haigang Cao,Xiaoyu Zhang,Kuilong Huang,Xiao Li,Gongshe Yang,Xin’e Shi
Skeletal muscle is an important metabolic organ of the body, and impaired skeletal muscle differentiation can result in a wide range of metabolic diseases. It has been shown that microRNAs (miRNAs) play an important role in skeletal muscle differentiation. The aim of this study was to investigate the role of mmu-miR-324-5p in the differentiation of C2C12 myoblasts and lipid droplet deposition in myotubes for future targeted therapies. We found that mmu-miR-324-5p was highly expressed in mouse skeletal muscle. Overexpression of miR-324-5p significantly inhibited C2C12 myoblast differentiation while promoting oleate-induced lipid accumulation and β-oxidation in C2C12 myoblasts. Conversely, inhibition of mmu-miR-324-5p promoted C2C12 myoblast differentiation and inhibited lipid deposition in myotubes. Mechanistically, mmu-miR-324-5p negatively regulated the expression of long non-coding Dum (lncDum) and peptidase M20 domain containing 1 (Pm20d1) in C2C12 myoblasts. Reduced lncDum expression was associated with a significant decrease in the expression of myogenesis-related genes. Knockdown of mmu-miR-324-5p increased the levels of lncDum and myogenesis-related gene expression. Following oleate-induced lipid deposition in C2C12 myoblasts, overexpression of mmu-miR-324-5p decreased the expression of Pm20d1 while increasing the expression of mitochondrial β-oxidation and long-chain fatty acid synthesis-related genes. In conclusion, we provide evidence that miR-324-5p inhibits C2C12 myoblast differentiation and promotes intramuscular lipid deposition by targeting lncDum and Pm20d1, respectively.
研究领域:
分子生物学
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细胞生物学
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肌肉生理学
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代谢
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DOI
PubMed
高影响因子
American Journal of Rhinology & Allergy
·
2021
·
IF 2.467
Zhiqi Ma,Haijuan Lian,Xiaoyan Lin,Yong Li
BackgroundAllergic rhinitis (AR) is one of the most common noninfectious respiratory diseases caused by immunoglobulin E (IgE) response.ObjectiveThe study sought to explore the relationship between lncRNA MIAT and miR-10b-5p and their interaction in the regulation of allergic phenotypes in allergic rhinitis (AR) mice.MethodsA mice model of AR was constructed using ovalbumin (OVA) sensitization. AR mice were treated with miR-10b-5p agomiR and LNA mediated lncRNA MIAT. The targeting relationship between MIAT and miR-10b-5p was analyzed by the ENCORI website and dual-luciferase reporter assay. The numbers of rubbing and sneezing of mice were counted. Hematoxylin-eosin (HE) staining visualized the eosinophils infiltration in nasal mucosa tissues of mice. The percentage of Th17 cells was quantitated by flow cytometry analysis. ELISA was used to detect the levels of serum OVA-specific IgE, the Th12 cytokine IL-4, and inflammatory cytokines (IL-6, IL-17).ResultsMIAT was up-regulated in the nasal mucosa of AR mice, while miR-10b-5p was down-regulated. MIAT directly suppressed miR-10b-5p expression in AR mice. The numbers of rubbing and sneezing, the percentage of Th17 cells, and the levels of OVA-specific IgE, IL-4, IL-6, and IL-17 in AR mice were decreased by miR-10b-5p overexpression, which was reversed by MIAT overexpression. The eosinophils infiltration in AR mice was inhibited by miR-10b-5p overexpression, which was also reversed by MIAT overexpression.ConclusionThe present study demonstrates that MIAT overexpression Promotes allergic inflammation and symptoms by activating Th17 immune response via miR-10b-5p inhibition.
研究领域:
免疫学
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分子生物学
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过敏
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DOI
PubMed
高影响因子
Journal of Materials Chemistry C
·
2022
·Vol. 10
·期 48
·18258-18263
·
IF 8.067
Li Ping Cao,Yao Wang,Yan Bai,Yong Jian Jiang,Chun Mei Li,Yuan Fang Li,Cheng Zhi Huang,Shu Jun Zhen
Owing to their simple and convenient synthesis, the application of metal–organic gels (MOGs) in fluorescence detection has been increasingly studied. However, most relevant studies are based on the fluorescence changes of MOGs themselves caused by the direct interaction between the target and MOG, resulting in limited universality and insufficient sensitivity and other shortcomings. Thus, we combined a Cu-based metal–organic gel (Cu-MOG) with an entropy-driven circuit (EDC), as an isothermal enzyme-free amplification technique, to detect miR-155 as a proof-of-principle target. The substrate for the EDC was designed as a three-strand duplex (TD) containing an output strand (OS) which was modified with 6-carboxyfluorescein (FAM). In the presence of the target, namely miR-155, the EDC was triggered and OS was released, making the OS transition from the hybrid state to the free state. The fluorescence of the FAM modified free OS strand was then quenched owing to the intramolecular photo-induced electron transfer (PET) of the new ground state complex formed between the OS and MOG with a quenching constant of 1.48 mL μg−1, which is much higher than that (0.08 mL μg−1) of the hybrid state OS. This method provided a dynamic detection range of 1 nM to 5 nM with a detection limit of 0.23 nM for miR-155, demonstrating that the Cu-MOG coupled EDC has promising applications in bioassays, and opens up a new application field of MOGs in EDC development.
研究领域:
分析化学
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生物传感器
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纳米技术
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分子生物学
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DOI
高影响因子
危险品化学品经营许可证（带存储）