ONCOGENE
·
2025
·
IF 7.3
Wei Xiaosong,Wang Beibei,Yang Yang,Fang Zhiwei,Yi Chengzhi,Zhang Liuhui,Fan Xin,Tang Dongdong,Zhang Lirong,Yang Xiaoming,Song Dongkui
Zinc finger protein 24 (ZNF24) is a conserved multifunctional transcription factor associated with tumorigenesis, but its function in bladder carcinogenesis remains unclear. Herein, the expression of ZNF24 was decreased in bladder cancer (BC) cells and tissues, and patients with higher expression of ZNF24 had a better prognosis. Doxycycline-induced overexpression and knockdown of ZNF24 identified its anti-proliferative and anti-metastasis role in BC in vitro and in vivo. The potential genes for the anti-cancer role of ZNF24, involving transcriptional regulation of several factors, such as dual-specificity phosphatase 1 and squalene epoxidase. E2 conjugating enzyme UBC9 and small ubiquitin-like modifier (SUMO) 1 were found to interact with ZNF24, suggesting that ZNF24 may be SUMOylated. Consistent with the expression, ZNF24 SUMOylation levels were decreased in BC cells and tissues. Pan-SUMOylation inhibition promoted protein degradation of ZNF24. UBC9 SUMOylated ZNF24 at Lys-27 (K27) site with SUMO1 modification and the K27 mutation of ZNF24 greatly damaged the protein stability of ZNF24. Cullin 3 (CUL3), a E3 ubiquitin ligase, was responsible for the degradation of ZNF24. ZNF24 SUMOylation prevented CUL3-mediated protein degradation of ZNF24. Overall, the crosstalk between the SUMOylation and ubiquitination of ZNF24 may be a novel regulatory mechanism to block tumorigenesis and development of BC.
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 Microbiology
·
2024
·
IF 4
Jia Jianping,Chen Zhitao,Li Qingqing,Li Feifei,Liu Siru,Bao Guoliang
Astaxanthin has multiple physiological functions and is applied widely. The yeast Phaffia rhodozyma is an ideal source of microbial astaxanthin. However, the stress conditions beneficial for astaxanthin synthesis often inhibit cell growth, leading to low productivity of astaxanthin in this yeast. In this study, 1 mg/L melatonin (MT) could increase the biomass, astaxanthin content, and yield in P. rhodozyma by 21.9, 93.9, and 139.1%, reaching 6.9 g/L, 0.3 mg/g DCW, and 2.2 mg/L, respectively. An RNA-seq-based transcriptomic analysis showed that MT could disturb the transcriptomic profile of P. rhodozyma cell. Furthermore, differentially expressed gene (DEG) analysis show that the genes induced or inhibited significantly by MT were mainly involved in astaxanthin synthesis, metabolite metabolism, substrate transportation, anti-stress, signal transduction, and transcription factor. A mechanism of MT regulating astaxanthin synthesis was proposed in this study. The mechanism is that MT entering the cell interacts with components of various signaling pathways or directly regulates their transcription levels. The altered signals are then transmitted to the transcription factors, which can regulate the expressions of a series of downstream genes as the DEGs. A zinc finger transcription factor gene (ZFTF), one of the most upregulated DEGs, induced by MT was selected to be overexpressed in P. rhodozyma. It was found that the biomass and astaxanthin synthesis of the transformant were further increased compared with those in MT-treatment condition. Combining MT-treatment and ZFTF overexpression in P. rhodozyma, the biomass, astaxanthin content, and yield were 8.6 g/L, 0.6 mg/g DCW, and 4.8 mg/L and increased by 52.1, 233.3, and 399.7% than those in the WT strain under MT-free condition. In this study, the synthesis and regulation theory of astaxanthin is deepened, and an efficient dual strategy for industrial production of microbial astaxanthin is proposed.
研究领域:
微生物学
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生物化学
·
基因工程
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2019
·
IF 2.931
Dongxin Zhao,Kui Lu,Guangbin Liu,Juhong Hou,Libo Yuan,Li Ma,Jie Liu,Juan He
Polypeptides with finger-like structures can often intercalate into the grooves of DNA , thereby affecting DNA repair or activating gene transcription, both of which are crucial for the regulation of physiological processes. Their conserved amino acid sequence and simple structure have provided useful elements for the design and assembly of functional molecules. In this paper, using the C 2 H 2 zinc finger domain and the PEP-FOLD3 online simulation platform 11 polypeptides containing 22 amino acid residues were designed. In addition, the CD spectroscopy was combined with the fluorescence spectroscopy to study the polypeptide structures and their interaction with DNA. Results showed that although addition of zinc ions affected the polypeptide structure, particularly of the polypeptides A4, B1, and B3, zinc ion was not an essential factor for increasing polypeptide-DNA interactions. Our study revealed an increase in the interaction strength between mutated polypeptides and DNA, suggesting that mutations disrupt polypeptide structure, and polypeptides interact with DNA by groove and electrostatic binding. Mutations at the 12th and 15th amino acid residues had the greatest effect. The stronger binding between A2 or B2 and DNA indicates that the polypeptide has a spatial structure that can stably interact with DNA. The structure and characteristics of these polypeptide domains can provide information for the design and development of new polypeptide functional molecules, which could have potential significance and applications. However, this information also suggests that there are many challenges facing polypeptide design due to the synergistic effects between the side chains of amino acid residues.
研究领域:
生物化学
·
分子生物学
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DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2021
·Vol. 45
·期 8
·1710-1719
·
IF 3.612
Yulan Gu,Chuandan Wan,Guoqiang Zhou,Jinlian Zhu,Zhiliang Shi,Zhixiang Zhuang
Gastric cancer (GC) is a kind of malignancy originating from the epithelium of gastric mucosa. Long noncoding RNAs (lncRNAs) are tightly related to the GC progression. Herein, our research was meant to investigate a novel lncRNA thymidylate synthetase opposite strand ( TYMSOS ) in GC. Quantitative real-time polymerase chain reaction was used to analyze TYMSOS expression in GC cells. 5-Ethynyl-2ʹ-deoxyuridine, flow cytometry analysis, and transwell assay detected the influence of TYMSOS on GC cell proliferation, apoptosis, migration, and invasion. Subcellular fractionation and fluorescent in situ hybridization assays determined the cellular localization of TYMSOS in GC cells. Bioinformatics programs, RNA-binding protein immunoprecipitation, RNA pull-down, and luciferase reporter assays measured the molecular interplays of TYMSOS in GC cells. In brief, TYMSOS was highly expressed in GC cells, and TYMSOS silence inhibited GC cell proliferation, migration, and invasion while elevating cell apoptosis. Functionally, TYMSOS functioned as a competing endogenous RNA to posttranscriptionally modulate GC progression. TYMSOS interacted with miR-4739 to regulate its target gene zinc finger protein 703 . Collectively, our study proved the tumor-promoting role of TYMSOS in GC cells, which might offer the utility value for GC treatment.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
Translational Oncology
·
2020
·
IF 3.558
Jie Cui,Jiatao Liu,Lulu Fan,Yue Zhu,Bei Zhou,Yu Wang,Wei Hua,Wei Wei,Guoping Sun
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Endoplasmic reticulum stress (ERS) is generally activated in HCC and is important for the sensitivity of HCC to anticancer drugs. ERS-dependent autophagy is a crucial mechanism affecting the sensitivity of HCC to anticancer drugs, but the mechanism by which ERS regulates autophagy is not well understood. Zinc finger protein 263 (ZNF263) is a transcription factor member of the zinc finger family. However, its functional role in HCC remains to be studied. In the current study, we investigated the role of ZNF263 in regulating ERS-induced chemoresistance in HCC and its possible mechanism. We found that ZNF263 was the most significant ERS-specific super-enhancer bounding transcriptional factor and was up-regulated in HCC patients and cell lines. Further, ZNF263 expression correlated with ERS, clinical stage and shorter survival in HCC patients. ZNF263 knockdown by RNA interference results in decreased proliferation, apoptosis resistance, and chemoresistance. Further study showed that ZNF263 increased chemoresistance by activating ERS-related autophagy. In conclusion, our study highlights ZNF263 as a functional ERS-related tumor activator and indicates it as a potential target for HCC therapy.
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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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL AND EXPERIMENTAL BOTANY
·
2018
·
IF 3.666
Yan-E Cheng,Ming-You Dong,Xian-Wei Fan,Li-Li Nong,You-Zhi Li
Soil salinity, commonly dominated by NaCl, is a major constraint to the production of food crops. Cassava ( Manihot esculenta ) is the most important tropical starch-producing crop. Reportedly, this crop is moderately sensitive to salt stress, and the A20/AN1-type zinc finger genes can confer abiotic stress tolerance to plants as the emerging target genes. However, neither cassava tolerance to salt nor the response of A20/AN1-type zinc finger genes from cassava to salt has yet to be characterized in detail. South China 124 (SC124), Fuxuan 01, South China 205, Kasetsart 50 and Argentina 7 (C4), somewhat differ in salt tolerance and starch content in storage roots under pre-established NaCl concentrations of 0, 10, 20, 30, 40, 50, 100, and 200 mM. In this study, we investigated responses of in vitro-grown plantlets of these five cultivars, focusing on plantlet growth, phytohormones, antioxidant enzymes, soluble protein and sugar, H 2 O 2 content, and expression of A20/AN1-type zinc finger genes. The major results were as follows: the growth of cassava was obviously inhibited, starting at 20 mM NaCl depending on the cultivars. All five cultivars could not grow at 100 mM NaCl; 10 mM NaCl caused promoted growth by increasing number, volume, surface area, viability, length of fibrous rootlets, and elongated root cells; 20 mM NaCl facilitated both accumulation of total starch in fibrous rootlets and increase in total protein content in shoots; increased growth and starch accumulation did not correlate with phytohormone levels, antioxidant enzyme activities between shoots and rootlets, or, consequently, in the whole plantlets; and the A20/AN1 gene family was composed of at least 11 members and their expression was induced or suppressed in rootlets of plantlets of pot-grown SC124 under 200 mM NaCl, depending on gene members. In conclusion, low salt (NaCl) can not only promote the cassava growth but also lead to accumulation of total starch in the fibrous rootlets and increase in total protein content in shoots instead of rootlets. Low salt promoting growth effects are likely associated with lower levels of abscisic acid and higher levels of gibberellin and indole-3-acetic acid under salt stress. Such antagonistic relationship among these three phytohormones maybe involves expression of A20/AN1 genes under salt stress. The demand for H 2 O 2 levels, osmoprotectants, and antioxidant enzyme activities in salt stress responses is cassava cultivar-dependent.
研究领域:
植物科学
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分子生物学
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农学
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DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2016
·
IF 7.441
Zihao Zhang,Jiaxun Wan,Luyan Sun,Yongjing Li,Jia Guo,Changchun Wang
Biodegradable materials used for drug delivery are of great demand due to their ability to degrade into low molecular weight species and further excrete from the body by metabolism. Herein, we report a new kind of zinc(II) crosslinked poly(methacrylic acid) nanohydrogels (ZCLNs) inspired by zinc finger proteins with dual stimuli-triggered degradation (glutathione and pH) for the first time. Compared with the disulfide bond crosslinked nanohydrogels, this new kind of ZCLNs is beneficial to the degradation of a wide range of cells, including normal cells. Ex vivo fluorescence images showed that the DOX-loaded folate-PEG conjugated zinc(II)-crosslinked polymeric nanohydrogels (FPZCLNs-15) preferentially accumulated in tumor tissue and the accumulation in normal tissues was much less compared with DOX-loaded PZCLNs-15 (non-targeted nanohydrogels) and free DOX , the FPZCLNs-15 (targeting system) delivered DOX to the tumor site with approximately 3.6- and 1.6-fold higher than free DOX and PZCLNs-15, respectively. Meanwhile, the PZCLNs-15 and FPZCLNs-15 reduced the concentration of DOX in the heart by 3.2- and 5.0-fold respectively, as compared to the free DOX. Moreover, a superior tumor growth inhibition and negligible damage to normal organs like the heart and kidney, which is reported to be vulnerable to DOX-associated side effects, are further demonstrated.
研究领域:
生物材料学
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肿瘤学
·
药剂学
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产品关联
DOI
PubMed
高影响因子
Andrology
·
2023
·
IF 4.5
Pan Gao,Xi Liu,Tianle Zhu,Rui Gao,Jingjing Gao,Yao Zhang,Hui Jiang,Houbao Huang,Xiansheng Zhang
Background Recently, dapoxetine has been widely accepted to treat premature ejaculation by fast-inhibiting 5-hydroxytryptamine reuptake. However, dapoxetine is not suitable for all premature ejaculation patients in clinical treatment. We need to investigate and reveal the mechanism deeply to solve this problem. Objectives To investigate and reveal the function of dopamine D4 receptor in dapoxetine medicated premature ejaculation treatment. Materials and methods A rat model was used to screen rapid ejaculators. The molecular mechanisms of histone serotonylation-mediated regulation of dopamine D4 receptor were demonstrated by chromatin immunoprecipitation, DNA pull-down, mass spectrometry analysis, and coimmunoprecipitation experiments. The biological function of dopamine D4 receptor was investigated through in vivo experiments by intrathecal injection of shDRD4 to knockdown dopamine D4 receptor. Results In this study, we found that dapoxetine increased expression of 5-hydroxytryptamine and dopamine D4 receptor. We demonstrated that dapoxetine increased levels of 5-hydroxytryptamine, which promoted histone serotonylation (H3K4me3Q5ser) and transcription factor myeloid zinc-finger 1 complex binding on the dopamine D4 receptor promoter, upregulated the expression of dopamine D4 receptor and thus delayed ejaculation. Discussion In this study, we demonstrated that dapoxetine increased the levels of 5-hydroxytryptamine, which promoted histone serotonylation and myeloid zinc-finger 1 complex binding to the dopamine D4 receptor promoter and upregulated the expression of dopamine D4 receptor, thus delaying ejaculation. Conclusion It is a novel mechanism that dapoxetine take effect of premature ejaculation treatment through upregulating the dopamine D4 receptor, which indicated that upregulated dopamine D4 receptor would enhance the dapoxetine effect in premature ejaculation treatment. This may lead to the development of novel therapeutic interventions for premature ejaculation.
研究领域:
药理学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2023
·Vol. 37
·期 10
·e23193
·
IF 4.8
Chaofan Wang,Yue Gao,Changjiao Luan,Wentao Sun,Sumin Ge,Yaru Li,Lei Xu,Qiu Du,Weili Liu,Guotao Lu,Weijuan Gong,Xingjie Ma
Cellular senescence is broadly known as a stable cell cycle arrest accompanied by a senescence-associated secretory phenotype (SASP). In the past decades, calcium signaling has emerged as a key mediator of cellular senescence. However, the transcriptional regulation of calcium signaling during cellular senescence remains partially understood. We have previously identified the nuclear receptor RXRA as a key senescence repressor through inhibiting the endoplasmic reticulum (ER) calcium release channel inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) mediated intracellular calcium signaling. Nevertheless, as a transcriptional recruiter, the mechanism by which RXRA inhibits ITPR2 during cellular senescence remains unclear. Here we identified the zinc finger protein ZBTB17 can interact with RXRA. Interestingly, knockdown of ZBTB17 induces a cascade of RXRA-dependent intracellular calcium signaling, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) accumulation, DNA damages, and ultimately cellular senescence. Moreover, the signaling and senescence phenotype induced by knocking down of ZBTB17 can also be abolished after silencing ITPR2. Altogether, our work provides a new mechanism controlling intracellular calcium signaling and cellular senescence and unveils novel insight toward the role of zinc finger proteins.
研究领域:
细胞生物学
·
分子生物学
·
转录调控
·
信号传导
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DOI
PubMed
高影响因子
CONNECTIVE TISSUE RESEARCH
·
2023
·
IF 2.9
Gao-Feng Zhao,Le-Bin Huang
Aims Osteoarthritis (OA) is a chronic inflammatory disease, characterized by degradation of extracellular matrix, apoptosis of chondrocytes and inflammation in articular cartilage. Zinc finger E-box binding homebox 2 (ZEB2), a transcription repressor, has been demonstrated with anti-inflammatory role in some cells. The analysis from GEO data reveals that ZEB2 expression is upregulated in articular cartilage of OA patients and experimental OA rodents. This study aims to confirm the function of ZEB2 in OA process.Material and methods The experimental OA was induced by anterior cruciate ligament transaction (ACLT) in rats, and the adenovirus loaded with ZEB2 coding sequence was intra-articularly injected into rats (1 × 10 PFU). The primary articular chondrocytes were stimulated by interleukin-1β (IL-1β) (10 ng/ml) to mimic the osteoarthritic injury, and transfected with the adenovirus carrying ZEB2 coding or silencing sequence. The apoptosis, content of extracellular matrix, inflammation, and the activity of NFκB signaling in chondrocytes and cartilage were determined.Results ZEB2 was highly expressed in osteoarthritic cartilage tissues and IL-1β-treated chondrocytes. The overexpression of ZEB2 restrained ACLT- or IL-1β administration-induced apoptosis, matrix degradation and inflammation in vivo or in vitro, evidenced by changed levels of cleaved caspase-3/PARP, collagen-II, aggrecan, matrix metalloproteinase 3/13, tumor necrosis factor-α and interleukin-6. Additionally, the phosphorylation of NFκB p65, IκBα and IKKα/β, and the nuclear translocation of p65 was blocked by ZEB2, implying inactivation of this signaling.Conclusions ZEB2 mitigated osteoarthritic symptoms in rats and chondrocytes, and NFκB signaling might be involved. These findings may provide novel insights for clinical treatment of OA.
研究领域:
骨科
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分子生物学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2023
·Vol. 46
·期 2
·209-218
·
IF 2
Chenhao Li,Cuizhi Geng
Triple-negative breast cancer (TNBC) puts a great threat to women’s health. GLIS family zinc finger 3 (GLIS3) belongs to the GLI transcription factor family and acts as a critical factor in cancer progression. Nevertheless, the part of GLIS3 played in TNBC is not known. Immunohistochemical (IHC) staining analysis displayed that GLIS3 was highly expressed in TNBC tissues. The effect of GLIS3 on the malignant phenotype of TNBC was tested in two different cell lines according to GLIS3 regulation. Upregulation of GLIS3 promoted the proliferation, migration, and invasion of TNBC cell lines, whereas the knockdown of GLIS3 suppressed these tumor activities. Inhibition of GLIS3 induced TNBC cell apoptosis. Furthermore, study as immunofluorescence and electrophoretic mobility shift assay confirmed that the nuclear factor-κB (NF-κB) signaling pathway activated by GLIS3 played an important role in TNBC cells’ malignant phenotype. In conclusion, the present work demonstrated that GLIS3 acts as a crucial element in TNBC progression via activating the NF-κB signaling pathway. Accordingly, above mentioned findings indicated that modulation of GLIS3 expression is a potential tactic to interfere with the progression of TNBC.
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
·
癌症研究
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DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2019
·
IF 3.119
Liting Wu,Enxu Zhou,Along Gao,Linghe Kong,Siwei Wu,Xia Bian,Yuan Li,Bingxi Li,Shengli Fu,Zheng Guo,Jianmin Ye
B lymphocyte-induced maturation protein 1 (Blimp-1), a transcription factor containing zinc finger , is required and sufficient to trigger terminal differentiation of B cells in mammals. The Blimp-1 ( OnBlimp-1 ) from Nile tilapia ( Oreochromis niloticus ) was identified and characterized its expression pattern during B cell activation and maturation. The cDNA of OnBlimp-1 open reading frame is 2547 bp encoding a protein of 848 amino acids and the predicted molecular weight is 93.36 kDa. OnBlimp-1 contains a SET domain and five ZnF_C2H2 domains, which shares high homology with that of other species. OnBlimp-1 transcription was detected in all examined tissues with high expression in the spleen (SPL). Analysis of sorted lymphocyte populations , including IgM + and IgM − cells from peripheral blood (PBL), SPL and anterior kidney (AK), indicated that the OnBlimp-1 transcription was highly expressed in the IgM + B cells. Upon LPS stimulation, OnBlimp-1 expression was up-regulated in tissues of PBL, SPL and AK significantly. The expression of OnBlimp-1 , as well as the secreted IgM , was significantly up-regulated in the SPL and AK leukocytes stimulated with anti-OnIgM monoclonal antibody and LPS in vitro , respectively. Above results suggest that OnBlimp-1, a cytokine regulating the terminal differentiation of activated B cells to antibody-secreting cells, is likely to play important roles in B cell activation and maturation in Nile tilapia.
研究领域:
免疫学
·
分子生物学
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鱼类生理学
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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）