CELL BIOLOGY INTERNATIONAL
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2022
·Vol. 46
·期 11
·1900-1914
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IF 4.473
Bin Xie,Feng Peng,Fengping He,Yixing Cheng,Jiangtao Cheng,Zhibing Zhou,Wei Mao
Ras-association domain family 1A (RASSF1A) is one of the most methylated genes in lung cancer (LC). We investigate whether the high DNA methylation level of RASSF1A can relieve the resistance of RASSF1A to LC by inhibiting RASSF1A's transcription factor binding to RASSF1A. RASSF1A expression in tissues and cells was tested utilizing quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. RASSF1A expression and RASSF1A methylation level in LC cells exposed to 5-Aza-dc were assessed by qRT-PCR and quantitative methylation-specific PCR. The association between CTCF and RASSF1A was assessed using hTFtarget, ChIP, and luciferase reporter gene analysis. The effects of 5-Aza-dc, CTCF, and RASSF1A on cell biological behaviors and epithelial-mesenchymal transition (EMT)-related markers were assessed by cell function experiments and Western blot. Moreover, we constructed the xenograft tumor and pulmonary nodule metastasis models, and assessed tumor volume and weight. RASSF1A expression and pulmonary nodule metastasis were tested utilizing qRT-PCR, Western blot, and H&E staining. RASSF1A was under-expressed in LC tissues and cells. 5-Aza-dc enhanced RASSF1A level and weakened RASSF1A methylation level in LC cells. RASSF1A silencing neutralized 5-Aza-dc-mediated repressing effects on LC cell biological function and EMT. The loss of CTCF binding to RASSF1A in LC cells was associated with DNA methylation. The effect of 5-Aza-dc on RASSF1A level, LC cell malignant behaviors, and EMT-related factors were strengthened by CTCF upregulation. RASSF1A overexpression suppressed LC tumor growth and pulmonary nodule metastasis in vivo. DNA methylation blocked the modulation of RASSF1A expression by CTCF and relieved the resistance of RASSF1A to LC.
研究领域:
癌症生物学
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分子生物学
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表观遗传学
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PubMed
高影响因子
CELL DEATH AND DIFFERENTIATION
·
2023
·Vol. 30
·期 5
·1260-1278
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IF 12.4
Sun Ge,Wei Yuntao,Zhou Baosheng,Wang Manlin,Luan Ruina,Bai Yu,Li Hao,Wang Shan,Zheng Dantong,Wang Chunyu,Wang Shengli,Zeng Kai,Liu Shuchang,Lin Lin,He Mingcong,Zhang Qiang,Zhao Yue
The estrogen receptor alpha (ERα) signaling pathway is a crucial target for ERα-positive breast cancer therapeutic strategies. Co-regulators and other transcription factors cooperate for effective ERα-related enhancer activation. Recent studies demonstrate that the transcription factor CTCF is essential to participate in ERα/E2-induced enhancer transactivation. However, the mechanism of how CTCF is achieved remains unknown. Here, we provided evidence that BAP18 is required for CTCF recruitment on ERα-enriched enhancers, facilitating CTCF-mediated chromatin accessibility to promote enhancer RNAs transcription. Consistently, GRO-seq demonstrates that the enhancer activity is positively correlated with BAP18 enrichment. Furthermore, BAP18 interacts with SMARCA1/BPTF to accelerate the recruitment of CTCF to ERα-related enhancers. Interestingly, BAP18 is involved in chromatin accessibility within enhancer regions, thereby increasing enhancer transactivation and enhancer-promoter looping. BAP18 depletion increases the sensitivity of anti-estrogen and anti-enhancer treatment in MCF7 cells. Collectively, our study indicates that BAP18 coordinates with CTCF to enlarge the transactivation of ERα-related enhancers, providing a better understanding of BAP18/CTCF coupling chromatin remodeling and E-P looping in the regulation of enhancer transcription.
研究领域:
癌症生物学
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分子生物学
·
转录调控
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染色质结构
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DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Jialun Duan,Chunjie Bao,Ying Xie,Haitao Guo,Yixuan Liu,Jianwei Li,Rui Liu,Peishan Li,Jing Bai,Yan Yan,Limin Mu,Xueqi Li,Guiling Wang,Wanliang Lu
Clustered regularly interspaced short palindromic repeats (CRISPR) technology emerges a remarkable potential for cure of refractory cancer like metastatic breast cancer. However, how to efficiently deliver the CRISPR system with non-viral carrier remains a major issue to be solved. Here, we report a kind of targeted core-shell nanoparticles (NPs) carrying dual plasmids (pHR-pCas9) for precise CCCTC-binding factor (CTCF) gene insert to circumvent metastatic breast cancer. The targeted core-shell NPs carrying pHR-pCas9 can accomplish γGTP-mediated cellular uptake and endosomal escape, facilitate the precise insert and stable expression of CTCF gene, inhibit the migration, metastasis, and colonization of metastatic breast cancer cells. Besides, the finding further reveals that the inhibitory mechanism of metastasis could be associated with up-regulating CTCF protein, followed by down-regulating stomatin (STOM) protein. The study offers a universal nanostrategy enabling the robust non-viral delivery of gene-editing system for treatment of severe illness.
研究领域:
癌症生物学
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分子生物学
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纳米技术
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基因治疗
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DOI
PubMed
高影响因子
DIGESTIVE DISEASES AND SCIENCES
·
2022
·Vol. 68
·期 3
·778-790
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IF 3.487
Gu Dan,Cao Ting,Yi Shijie,Liu Ya,Fan Chao
Background Ulcerative colitis (UC) features chronic, non-infectious inflammation of the colon. Insulin-like growth factor binding protein 5 (IGFBP5) has been indicated to be related to various inflammation-related diseases. However, its association with UC remains largely unclear. Aims Here, we investigate the role of IGFBP5 in colonic mucosal epithelial cell injury in UC. Methods Differentially expressed genes in the colonic tissues of UC mice were screened using the Gene Expression Omnibus database, and IGFBP5 was identified. UC mice were developed using dextran sulfate sodium, and IGFBP5 expression in the colonic tissues of UC mice was confirmed by immunohistochemistry and RT-qPCR. The effects of IGFBP 5 in vivo and in vitro were investigated by intraperitoneal injection of adeno-associated virus into UC mice or by transfection with an IGFBP5 overexpression plasmid into lipopolysaccharide-treated colonic mucosal epithelial cells. The mechanisms causing IGFBP5 deletion in UC were predicted by bioinformatics analysis and ChIP-qPCR and verified by rescue experiments. Results IGFBP5 was reduced in UC. IGFBP5 impaired the NFκB pathway in the colonic tissue of UC mice and ameliorated inflammatory infiltration and colonic mucosal cell injury. IGFBP5 depletion was associated with H3K27me3 modification, which was induced by EZH2. CTCF was responsible for recruiting EZH2 to the promoter region of IGFBP5. CTCF inhibition repressed UC progression by reducing H3K27me3 modification via the discouragement of the enrichment of EZH2 in the IGFBP5 promoter. Conclusions CTCF modulates H3K27me3 modification of the IGFBP5 promoter by recruiting EZH2, thereby downregulating IGFBP5 to accentuate colonic mucosal epithelial cell injury in UC mice.
研究领域:
免疫学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2026
·
IF 10.6
Xinchao Guan,Lijie Xie,Guoliang Li,Yujie He,Shilin Chen,Han Wang,Wenke Yuan,Huan Gao,Ming Chen,Xiaoge Yang,Yingxia Luo,Xiaojian Shao,Wen Chen,Lili Liu,Qing Wang
NCM exposure is associated with lower Mini-Cog scores and higher NfL. • NCM may induce rat cognitive deficits, neuronal damage, and NMDAR downregulation. • CTCF is implicated in NCM metal ion induced impairment of NMDAR and synaptogenesis. • 4.Current Ni/Mn OELs may exceed the neurotoxicity threshold of NCM. Lithium nickel cobalt manganese oxide (NCM) is the predominant cathode material for lithium-ion batteries (LIBs); however, its occupational health risks remain insufficiently understood. In this study, we found that in occupationally NCM‑exposed workers, urinary levels of Li, Ni, Co, and Mn were negatively associated with Mini‑Cog test scores and positively associated with serum neurofilament light chain (NfL, as neuronal injury marker). In an intratracheal instillation rat model, NCM-exposed rats exhibited learning and memory deficits, neuronal injury, and reduced synaptic complexity. RNA‑seq analysis revealed suppression of N-methyl- D -aspartate receptors (NMDAR)‑dependent synaptogenesis pathways in rat hippocampus, along with downregulation of NMDAR subunits (GluN2A and GluN2B) and postsynaptic proteins such as CaMKII‑α, MAP2, PSD‑95, and Synapsin‑1. In SH-SY5Y cells, treatment with NCM-derived metals recapitulated these gene expression changes. Bioinformatics analysis identified CCCTC-binding factor (CTCF) as a potential regulator of NMDAR. Cellular thermal shift assays (CETSA) identified the binding of NCM-derived metals to CTCF. Based on in vivo data, human equivalent concentrations (HECs) derived from BMDL 10 of Ni and Mn were below the current OELs of China and America. Collectively, these findings indicate that NCM may induce neurotoxicity and impair learning and memory by disrupting synaptogenesis, and CTCF is implicated in this process. Download: Download high-res image (273KB) Download: Download full-size image
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高影响因子
NUCLEIC ACIDS RESEARCH
·
2020
·Vol. 48
·期 19
·10768-10784
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IF 11.502
Sun Ge,Wang Chunyu,Wang Shengli,Sun Hongmiao,Zeng Kai,Zou Renlong,Lin Lin,Liu Wei,Sun Ning,Song Huijuan,Liu Wensu,Zhou Tingting,Jin Feng,Shan Zhongyan,Zhao Yue
Estrogen receptor alpha (ERα) signaling pathway is essential for ERα-positive breast cancer progression and endocrine therapy resistance. Bromodomain PHD Finger Transcription Factor (BPTF) associated protein of 18kDa (BAP18) has been recognized as a crucial H3K4me3 reader. However, the whole genomic occupation of BAP18 and its biological function in breast cancer is still elusive. Here, we found that higher expression of BAP18 in ERα-positive breast cancer is positively correlated with poor prognosis. ChIP-seq analysis further demonstrated that the half estrogen response elements (EREs) and the CCCTC binding factor (CTCF) binding sites are the significant enrichment sites found in estrogen-induced BAP18 binding sites. Also, we provide the evidence to demonstrate that BAP18 as a novel co-activator of ERα is required for the recruitment of COMPASS-like core subunits to the cis-regulatory element of ERα target genes in breast cancer cells. BAP18 is recruited to the promoter regions of estrogen-induced genes, accompanied with the enrichment of the lysine 4-trimethylated histone H3 tail (H3K4me3) in the presence of E2. Furthermore, BAP18 promotes cell growth and associates the sensitivity of antiestrogen in ERα-positive breast cancer. Our data suggest that BAP18 facilitates the association between ERα and COMPASS-like core subunits, which might be an essential epigenetic therapeutic target for breast cancer.
研究领域:
肿瘤学
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分子生物学
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表观遗传学
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癌症治疗
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DOI
PubMed
高影响因子
Science Advances
·
2025
·Vol. 11
·期 35
·
IF 12.5
Juan Bai,Hanhan Wei,Siling Hu,Yi Guo,Qifan Zhang,Xiaokun Liu,Chenhuan Xu
The measurement of three-dimensional genome folding in the nucleus, mostly through Hi-C methods, is expressed as contact frequencies between genomic segments, without anchoring to physical axes of the spherical nucleus. Here, we mapped the chromatin contacts along nuclear radial axis and built radial score by factoring in contact frequencies. The chromatin high-order structures exhibit rich diversity along radial axis. Furthermore, the proximal trans contacts retrieved by radial score reveal conserved active/inactive chromatin segregation across intra- and interchromosomal interactions. Ablation of CTCF proteins disrupts chromatin loops with mild changes to chromatin radial positioning. By acutely perturbing multiple transcription factor (TF) occupancy, chromatin loop dissolutions are often accompanied by radial dissociations between two anchors. Our work provides a genome architecture reference map adhering to nuclear physical axis and suggests that multiple architectural TFs collectively shape nuclear positioning of chromatin and their contacts, with contacts serving as forces on chromatin positioning as well.
研究领域:
分子生物学
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基因组学
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细胞生物学
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表观遗传学
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生物信息学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Junxian Zhu,Yongchang Wang,Luo Lei,Chen Chen,Liqin Ji,Jiansong Li,Congcong Wu,Wenjun Yu,Laifu Luo,Weiqin Chen,Pan Liu,Xiaoyou Hong,Xiaoli Liu,Haigang Chen,Chengqing Wei,Xinping Zhu,Wei Li
A feature of the Chinese soft-shelled turtle ( Pelodiscus sinensis ) is seasonal spermatogenesis ; however, the underlying molecular mechanism is not well clarified. Here, we firstly cloned and characterized P. sinensis DKKL1 , and then performed comparative genomic studies, expression analysis, and functional validation. P. sinensis DKKL1 had 2 putative N-glycosylation sites and 16 phosphorylation sites. DKKL1 also had classic transmembrane structures that were extracellularly localized. DKKL1 's genetic distance was close to turtles, followed by amphibians and mammals, but its genetic distance was far from fishes. DKKL1 genes from different species shared distinct genomic characteristics. Meanwhile, they were also relatively conserved among themselves, at least from the perspective of classes. Notably, the transcription factors associated with spermatogenesis were also identified, containing CTCF , EWSR1 , and FOXL2 . DKKL1 exhibited sexually dimorphic expression only in adult gonads, which was significantly higher than that in other somatic tissues ( P < 0.001), and was barely expressed in embryonic gonads. DKKL1 transcripts showed a strong signal in sperm, while faint signals were detected in other male germ cells. DKKL1 in adult testes progressively increased per month ( P < 0.05), displaying a seasonal expression trait. DKKL1 was significantly downregulated in testes cells after the sex hormones (17β-estradiol and 17α-methyltestosterone) and Wnt/β-catenin inhibitor treatment ( P < 0.05). Likewise, the Wnt/β-catenin inhibitor treatment dramatically repressed CTCF, EWSR1, and FOXL2 expression. Conversely, they were markedly upregulated after the 17β-estradiol and 17α-methyltestosterone treatment, suggesting that the three transcription factors might bind to different promoter regions, thereby negatively regulating DKKL1 transcription in response to the changes in the estrogen and androgen pathways, and positively controlling DKKL1 transcription in answer to the alterations in the Wnt/β-catenin pathway. Knockdown of DKKL1 significantly reduced the relative expression of HMGB2 and SPATS1 ( P < 0.01), suggesting that it may be involved in seasonal spermatogenesis of P. sinensis through a positive regulatory interaction with these two genes. Overall, our findings provide novel insights into the genome evolution and potential functions of seasonal spermatogenesis of P. sinensis DKKL1 .
研究领域:
基因组学
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生殖生物学
·
分子生物学
·
比较基因组学
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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）