Microbial Biotechnology
·
2021
·Vol. 15
·期 1
·337-352
·
IF 5.813
Luoyi Zhu,Jie Fu,Xiao Xiao,Fengqin Wang,Mingliang Jin,Weihuan Fang,Yizhen Wang,Xin Zong
Summary Faecal Microbiota Transplantation (FMT) is considered as a promising technology to fight against obesity. Wild boar has leanermuscle and less fat in comparison to the domestic pig, which were thought to be related with microbiota. To investigate the function and mechanism of the wild boar microbiota on obesity, we first analysed the wild boar microbiota composition via 16S rDNA sequencing, which showed that Firmicutes and Proteobacteria were the dominant bacteria. Then, we established a high-fat diet (HFD)-induced obesity model, and transfer low and high concentrations of wild boar faecal suspension in mice for 9 weeks. The results showed that FMT prevented HFD-induced obesity and lipid metabolism disorders, and altered the jejunal microbiota composition especially increasing the abundance of the Lactobacillus and Romboutsia , which were negatively correlated with obesity-related indicators. Moreover, we found that the anti-obesity effect of wild boar faecal suspension was associated with jejunal N6-methyladenosine (m 6 A) levels. Overall, these results suggest that FMT has a mitigating effect on HFD-induced obesity, which may be due to the impressive effects of FMT on the microbial composition and structure of the jejunum. These changes further alter intestinal lipid metabolism and m 6 A levels to achieve resistance to obesity.
研究领域:
微生物学
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营养学
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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
Cell Death & Disease
·
2024
·Vol. 15
·期 10
·1-16
·
IF 8.1
Wan Xinyi,Zeng Weiwu,Fan Haonan,Wang Chenliang,Han Shixun,Sun Zhongxing,Tang Mei,Shao Juejia,Liu Yu,Fang Yuan,Jia Junqi,Tang Yin,Zhang Yanjun,Zhao Bin,Fang Dong
MAT2B works together with MAT2A to synthesize S-Adenosyl methionine (SAM) as the primary methyl donor. MAT2B, despite lacking catalytic activity, exerts regulatory control over the enzymatic activity of MAT2A. In addition to the enzymatic activity regulation, we find that, in an NADP + -dependent manner, MAT2B binds and stabilizes MAT2A. Disruption of the cellular NADP + remodels the protein level of MAT2A. The pentose phosphatase pathway regulates the level of MAT2A protein through the interaction of NADP + with MAT2B. Additionally, MAT2B-MAT2A interaction regulates the mRNA m6A modification and stability. In liver tumors, the Mat2a mRNA level is elevated but the protein level is decreased by the restricted NADP + . Blocking the interaction between MAT2B and MAT2A by the keto diet can suppress liver tumor growth. These findings reveal that MAT2B is essential for regulating the protein levels of MAT2A and connecting SAM synthesis to mRNA m6A.
研究领域:
癌症生物学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 40
·
IF 11.7
Lian Cui,You Wu,Zeyu Chen,Bingjie Li,Jiangluyi Cai,Zhanhe Chang,Weide Xiao,Yuanyuan Wang,Nan Yang,Yu Wang,Zengyang Yu,Lingling Yao,Rui Ma,Xin Wang,Youdong Chen,Qianyu Chen,Hao Mei,Zhiyi Lan,Yingyuan Yu,Rongfen Chen,Xingbiao Wu,Qian Yu,Jiajing Lu,Ning Yu,Xilin Zhang,Jun Liu,Lingjuan Zhang,Yuping Lai,Shaorong Gao,Yawei Gao,Chunyuan Guo,Yuling Shi
Disrupted N6-methyladenosine (m6A) modification modulates various inflammatory disorders. However, the role of m6A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m6A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m6A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m6A modification–lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m6A modulators to attenuate inflammatory skin diseases.
研究领域:
免疫学
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分子生物学
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皮肤病学
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DOI
PubMed
高影响因子
DIABETES
·
2023
·Vol. 72
·期 8
·1083-1094
·
IF 7.7
Xie Renxiang,Yan Sujun,Zhou Xiaoling,Gao Yunyi,Qian Yu,Hou Jingyu,Chen Zhanghui,Lai Kairan,Gao Xiangwei,Wei Saisai
The induction of beige adipocytes in white adipose tissue (WAT), also known as WAT beiging, improves glucose and lipid metabolism. However, the regulation of WAT beiging at the posttranscriptional level remains to be studied. Here, we report that METTL3, the methyltransferase of N6-methyladenosine (m 6 A) mRNA modification, is induced during WAT beiging in mice. Adipose-specific depletion of the Mettl3 gene undermines WAT beiging and impairs the metabolic capability of mice fed with a high-fat diet. Mechanistically, METTL3-catalyzed m 6 A installation on thermogenic mRNAs, including Krüppel-like factor 9 ( Klf9 ), prevents their degradation. Activation of the METTL3 complex by its chemical ligand methyl piperidine-3-carboxylate promotes WAT beiging, reduces body weight, and corrects metabolic disorders in diet-induced obese mice. These findings uncover a novel epitranscriptional mechanism in WAT beiging and identify METTL3 as a potential therapeutic target for obesity-associated diseases. Article Highlights METTL3, the methyltransferase of N6-methyladenosine (m 6 A) mRNA modification, is induced during WAT beiging. Depletion of Mettl3 undermines WAT beiging and impairs thermogenesis. METTL3-mediated m 6 A installation promotes the stability of Krüppel-like factor 9 ( Klf9 ). KLF9 rescues impaired beiging elicited by Mettl3 depletion. Pharmaceutical activation of the METTL3 complex by its chemical ligand methyl piperidine-3-carboxylate induces WAT beiging. Methyl piperidine-3-carboxylate corrects obesity-associated disorders. The METTL3-KLF9 pathway may serve as a potential therapeutic target for obesity-associated diseases.
研究领域:
分子生物学
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代谢
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肥胖研究
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表观遗传学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yangcenzi Xie,Wenqian Tian,Chao Zheng,Ming Li
RNA N 6 -methyladenosine (m 6 A) modification plays critical roles in diverse biological processes and human diseases, but its functional studies are greatly impeded by the inability to quantify the m 6 A methylation in whole-transcriptomes. Here, An integrated label-free surface-enhanced Raman spectroscopy (SERS) profiling strategy, named m 6 A-SERS-profiler, is developed for quantitative transcriptome-wide m 6 A detection of cellular and serum RNA. The m 6 A-SERS-profiler is rationally designed through coupling the plasmonic liquid microparticle-based label-free SERS biosensing with the custom deep learning-assisted spectral analysis of m 6 A methylation signatures. With this m 6 A-SERS-profiler, direct identification of SERS spectral signatures of canonical nucleoside monophosphates and N 6 -methyladenosine 5′-monophosphate is achieved. The applicability of the m 6 A-SERS-profiler is verified by quantifying the m 6 A methylation status of microRNA and natural RNA in total RNA isolated from cancer cells and clinical serums. The results reveal a significant difference in the m 6 A RNA methylation among breast cancer cells of different subtypes and between clinical serums from healthy individuals and breast cancer patients. Moreover, the method can quantitatively track the m 6 A dynamics in cancer cells caused by pharmacological inhibition of the m 6 A methyltransferase. Thus, this m 6 A-SERS-profiler holds great promise for transcriptome-wide quantitative detection of m 6 A RNA methylation to investigate biological functions and dynamics of m 6 A methylation in human diseases.
研究领域:
生物化学
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分子生物学
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生物物理学
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癌症研究
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分析化学
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产品关联
DOI
高影响因子
eLife
·
2025
·
IF 0
Chong Zhang,Zuoyan Zhang,Yueyi Wu,Yuchen Wu,Jing Cheng,Kaizhi Luo,Zhidi Li,Manman Zhang,Jian Wang,Xuesen Zhang,Yangling Li
Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and the prognosis is poor due to distant metastasis. Thus, there is an urgent need to discover novel therapeutic targets and strategies to overcome metastasis. A series of in vitro and in vivo phenotype experiments were performed to investigate the role of phosphodiesterase 1A (PDE1A) in NSCLC. The RNA binding protein immunoprecipitation (RIP) assay, messenger RNA (mRNA) stability assay, and LC-MS/MS were performed to investigate the molecular mechanisms of PDE1A in NSCLC progression. PDE1A has been shown to promote metastasis and epithelial-mesenchymal transition (EMT) progression of NSCLC. In addition, NSCLC cells overexpressing PDE1A promoted angiogenesis by regulating exosome release. IL-6/JAK/STAT3 signaling pathway was highly enriched in PDE1A-coexpressed genes, and PDE1A promoted NSCLC metastasis by activating the STAT3 pathway. GO enrichment analysis of PDE1A-interacting genes showed that PDE1A might interact with YTHDF2 and participate in m6A-containing RNA binding. The binding between PDE1A and YTHDF2 was verified, and PDE1A regulated the STAT3 pathway by interacting with YTHDF2. The mechanism of the YTHDF2/PDE1A complex in regulating the STAT3 pathway was predicted by overlapping YTHDF2-interacting RNAs and genes coexpressed with YTHDF2 and STAT3. The interactions between YTHDF2 and target mRNAs were predicted, and there were three predicted targets of YTHDF2 with high scores: NRF2, SOCS2, and MET. Indeed, PDE1A interacted with YTHDF2, destabilized SOCS2, and activated the STAT3 pathway. Mechanistic data uncover a novel PDE1A/YTHDF2/STAT3 axis driving NSCLC metastasis and suggest potential therapeutic strategies for metastatic disease.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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生物化学
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信号转导
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RNA生物学
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肿瘤学
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产品关联
DOI
PubMed
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Weiwei Wang,Xin Li,Qiuhui Qian,Jin Yan,Haishan Huang,Xuedong Wang,Huili Wang
Because triclosan (TCS) has been confirmed to cause severe neurotoxicity, it is urgent to disclose the underlying toxicity mechanisms at varying levels. TCS exposure resulted in a series of malformations in larval zebrafish, including reduced neurons, blood-vessel ablation and abnormal neurobehavior. Apoptosis staining and the upregulated expression of proapoptotic genes demonstrated that TCS induced neuronal apoptosis and neurotransmitter disorders. By integrating RT-qPCR analysis with the effects of pathway inhibitors and agonists, we found that TCS triggered abnormal regulation of neuron development-related functional genes, and suppressed the BDNF/TrkB signaling pathway. TCS inhibited total m 6 A-RNA modification level by activating the demethylase ALKBH5, and induced neurodevelopmental toxicity based on the knockdown experiments of alkbh5 and molecular docking . The main novelties of this study lies in: (1) based on specific staining and transgenic lines, the differential neurotoxicity effects of TCS were unravelled at individual, physiological, biochemical and molecular levels in vivo ; (2) from a epigenetics viewpoint, the decreasing m 6 A methylation level was confirmed to be mediated by alkbh5 upregulation; and (3) both homology modeling and molecular docking evidenced the targeting action of TCS on ALKBH5 enzyme. These findings open a novel avene for TCS’s risk assessment and early intervention of the contaminant-sourcing diseases.
研究领域:
毒理学
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神经科学
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分子生物学
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表观遗传学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOTECHNOLOGY
·
2023
·
IF 2.6
Lv Chen-Guang,Cheng Yao,Zhang Lei,Wu Guo-Gang,Liang Chun-Yan,Tao Zuo,Chen Bo
BC (breast cancer) is the leading cause of cancer death in women. Exosome component 2 (EXOSC2), an RNA exosome component, is elevated in BC tissues and may relate to BC carcinogenesis. In this work, the high EXOSC2 expression was correlated with TNM (Tumor Node Metastasis) stage. Moreover, overexpression of EXOSC2 enhanced tumorigenic capacity of BC cells via facilitating cell proliferation and cell cycle progression, increasing migration and angiogenesis, as well as exacerbating xenograft formation in vivo. Whereas, EXOSC2 knockdown showed anti-cancer effects, including inhibition of cell proliferation and angiogenesis. Mechanistically, EXOSC2 activated the wnt/β-catenin pathway, which was also abolished by EXOSC2 knockdown. In addition, there were m6A methylation modification sites in the mRNA of EXOSC2. WTAP (Wilms tumor 1-associated protein) bound to EXOSC2 mRNA and increased its m6A methylation, resulting in extending the half-life of EXOSC2 mRNA. Luciferase data also confirmed that WTAP enhanced EXOSC2 mRNA stability through binding with the 3′-UTR containing m6A sites. Furthermore, WTAP silencing exhibited cancer-inhibiting effects on cell viability, cell cycle progression and tube formation, which was effectively reversed by EXOSC2 overexpression. In conclusion, our results demonstrate that EXOSC2 promotes the malignant behaviors of BC cells via activating the wnt/β-catenin pathway. In addition, EXOSC2 mediates the function of WTAP which contributes to the m6A modification of EXOSC2. Totally, this study suggested that EXOSC2 mediated the pro-tumor role of WTAP via activating the wnt/β-catenin signal.
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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癌症生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
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IF 8.7
Bingbing Sun,Wanwan Zhang,Meisheng Yi,Kuntong Jia
N 6 -methyladenosine (m 6 A) modification plays crucial roles in diverse cellular processes, including the regulation of innate immune responses; however, its specific role in antiviral defense mechanisms in aquatic organisms remains incompletely understood. This study identifies LjMETTL14, a core m 6 A methyltransferase in sea perch ( Lateolabrax japonicus ), as a key regulator of antiviral immunity against nervous necrosis virus (NNV), a major pathogen threatening aquaculture. Our findings show that LjMETTL14 expression was significantly upregulated in response to NNV infection, and overexpression of LjMETTL14 suppresses viral replication by enhancing retinoic acid-inducible gene I-like receptor (RLRs) signaling and type I interferon (IFN) production. In contrast, LjMETTL14 knockdown leads to impaired RLRs signaling and markedly increased viral replication, underscoring its essential antiviral function. Mechanistically, LjMETTL14 interacts specifically with transmembrane domain of mitochondrial antiviral signaling protein (LjMAVS), promoting its m 6 A methylation, protein stability, and multimeric aggregation, thereby enhancing LjMAVS-mediated type I IFN signaling. Conversely, NNV capsid protein (CP) interacts with LjMETTL14, suppressing its expression and impeding the LjMAVS-dependent IFN response, thereby facilitating viral replication. These findings reveal a novel epitranscriptomic regulatory mechanism involving LjMETTL14 and LjMAVS that orchestrates antiviral immunity in fish, highlighting LjMETTL14 as a potential therapeutic target for controlling NNV infection in aquaculture.
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DOI
PubMed
高影响因子
Applied Biological Chemistry
·
2025
·Vol. 68
·期 1
·1-11
·
IF 2.7
Dou Yufeng,Yang Jiao,Huang Na,Lu Xiaoxiao,Yan Liping
Background Pneumonia is a serious respiratory disease that significantly impacts human health. Quercetin (QUE), a plant extract, has been shown to exert protective effects against lung injury, but its precise mechanisms remain unclear. Methods Lipopolysaccharide (LPS) was used to induce injury in embryonic lung fibroblasts. Cell viability, proliferation, and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, 5-ethynyl-2’-deoxyuridine (EdU) staining, and flow cytometry assay, respectively. Reactive oxygen species (ROS), malondialdehyde (MDA), and Fe 2+ levels were evaluated using corresponding assay kits. The levels of inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR (qRT-PCR) and western blot were employed to analyze the expression and correlation of related genes. Methylated RNA immunoprecipitation (MeRIP) was employed to verify the regulatory mechanism between genes. Results QUE inhibited embryonic lung fibroblast injury. Both transducin β-like 1 X-linked receptor 1 (TBL1XR1) and methyltransferase 3 (METTL3) were highly expressed in lung injury tissues and cells, which were decreased by QUE treatment. TBL1XR1 deficiency weakened LPS-induced embryonic lung fibroblast injury. Mechanistically, METTL3 mediated the N 6 -methyladenosine (m6A) methylation and stabilized the TBL1XR1 mRNA. TBL1XR1 up-regulation alleviated the retardation of METTL3 absence on embryonic lung fibroblast injury. Furthermore, METTL3 overexpression reversed the inhibition of QUE on embryonic lung fibroblast injury. Conclusion QUE inhibited embryonic lung fibroblast injury by regulating the METTL3-mediated m6A methylation of TBL1XR1 mRNA.
研究领域:
分子生物学
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药理学
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呼吸医学
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表观遗传学
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细胞生物学
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产品关联
DOI
高影响因子
Materials Today Nano
·
2022
·
IF 13.364
X. Cui,Y. Zhou,Y. Zheng,L. Cao,L. Gao,J. Duan,H. Yin,S. Ai
N 6 -methyladenosine (m 6 A) is the most abundant and dynamic reversible modification of mRNA in eukaryotes discovered in the mid-1970s, which is widely involved in various physiological processes. Fat mass and obesity-associated protein (FTO protein) is not only a demethylase for m 6 A, but also a carcinogenic factor for many human cancers. Therefore, it is very important to build a simple and sensitive platform for simultaneous detection of m 6 A and FTO protein. To achieve this aim, a novel photoelectrochemical biosensor was constructed with the antibody-free detection strategy of DTT mediated –SH functionalization of m 6 A triggered by FTO protein catalyzed m 6 A oxidation . To achieve high detection sensitivity, CdS/Bi 2 MoO 6 /MoSe 2 system with matched energy gap was employed as photoactive material. To achieve high detection selectivity , the –CH 3 of m 6 A in the captured RNA sequence (m 6 A RNA) on the electrode surface was oxidized by FTO protein to form hydroxymethyl, followed with the covalent reaction of DTT with hydroxymethyl, making the labeling of m 6 A with –SH. Finally, a CdS nanoparticle was modified on the electrode through the specific covalent reaction between –SH and Cd, achieving the improvement of the photocurrent with the matched energy band . Under the optimal experimental conditions, the biosensor showed linear range from 0.001 to 50 nM and 0.0005–500 μg/L with the detection limit of 0.37 pM and 0.034 ng/L (S/N = 3) for m 6 A RNA and FTO protein, respectively. The applicability of the developed method was assessed by investigating the effect of entacapone on FTO protein activity.
研究领域:
生物化学
·
分析化学
·
生物技术
·
癌症研究
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产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Taorong Shen,Xing Huang,Yanfei Zhang,Yanli Tong,Yakun Shi,Jianhe Guo,Xiaoyong Zou,Yuzhi Xu,Zong Dai
Fat mass and obesity-associated protein (FTO) plays a crucial role in regulating the dynamic modification of N6-methyladenosine (m6A) in eukaryotic mRNA. Sensitive detection of the FTO level and efficient evaluation of the FTO demethylase activity are of great importance to early cancer diagnosis and anticancer drug discovery, which are currently challenged by limited sensitivity/precision and low throughput. Herein, a robust strategy based on the dephosphorylation switch DNAzyme-rolling circle amplification (RCA) circuit, termed DSD-RCA, is developed for highly sensitive detection of FTO and inhibitor screening. Initially, the catalytic activity of DNAzyme is silenced by engineering with an m6A modification in its catalytic core. Only in the presence of target FTO can the methyl group on DNAzyme be eliminated, resulting in the activation of the catalytic activity of DNAzyme and thus cleaving the hairpin substrate to release numerous primers. Different from the conventional methods that use the downstream cleavage primer with the original 3′-hydroxyl end directly as the RCA primer with the problem of high background signal, which should be compensated by additional separation and wash steps in heterogeneous format, our DSD-RCA assay uses the upstream cleavage primer with a 2′,3′-cyclic phosphate terminus at the 3′-end serving as an intrinsically blocked 3′ end. Only after a dephosphorylation reaction mediated by T4 polynucleotide kinase can the upstream cleavage primers with a resultant 3′-hydroxyl end be extended by RCA. With the high signal-to-noise ratio and homogeneous property, the proposed platform can sensitively detect FTO with a limit of detection of 31.4 pM, and the relative standard deviations (RSDs %) ranging from 0.8 to 2.0% were much lower than the heterogeneous methods. The DSD-RCA method was applied for analyzing FTO in cytoplasmic lysates from different cell lines and tissues of breast cancer patients and further used for screening FTO inhibitors without the need for separation or cleaning, providing an opportunity for achieving high throughput and demonstrating the potential applications of this strategy in disease diagnostics, drug discovery, and biological applications.
研究领域:
生物化学
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分子生物学
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癌症研究
·
药物发现
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）