Reproductive Biology
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2022
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IF 2.089
Zhongxue Ye,Yafen Jiang,Junlong Wu
This study intends to investigate the effects of DNA methyltransferase 3B (DNMT3B) and ten-eleven translocation 3 (TET3) on transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in ovarian cancer (OV) cells. According to the specific experiments, the cells were treated with TGF-β1 for 48 h, and then the expressions of EMT-related proteins (E-cadherin, Vimentin and Snail), TET3 and DNMT3B were quantified by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Methprimer, methylation-specific PCR (MSP), bisulfite sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) were used to determine the regulation of DNMT3B on TET3 promoter. The impacts of DNMT3B and TET3 upon the EMT-related proteins and OV cell migration and invasion abilities were evaluated through the rescue experiments and the loss- and gain-of-function experiments. In line with the results, TGF-β1 down-regulated TET3 and E-cadherin levels, up-regulated Vimentin and Snail levels, promoted migratory and invasive abilities, and increased methylation level of TET3 promoter in OV cells, which however were reversed by shDNMT3B. The binding of DNMT3B to TET3 promoter facilitated the methylation of TET3 promoter. Overexpressed TET3 inhibited the migratory and invasive abilities and EMT of OV cells, whereas shTET3 did the opposite. ShTET3 also offset the regulatory effects of shDNMT3B on EMT, migration and invasion of OV cells. To conclude, DNMT3B mitigates the suppression of TET3 on TGF-β1-induced EMT in OV cells by methylating the promoter region of TET3.
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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DOI
PubMed
高影响因子
MEDICAL ONCOLOGY
·
2025
·Vol. 42
·期 8
·1-13
·
IF 3.5
Cai Zhiren,Xie Yanqi,Li Luyao,Zheng Yuhang,Zhou Xianghui,Zhou Guanghua,Wang Ganping,Zeng Xin
Bladder cancer is a major health concern, and understanding its molecular mechanisms is essential for developing effective therapies. TET3, a DNA hydroxymethylase, has been linked to tumor progression, but its role in bladder cancer remains unclear. We analyzed single-cell RNA sequencing data and identified TET3 as a key regulator in tumor-promoting cells using scissor analysis. Functional experiments were performed to evaluate the effects of TET3 knockdown on cell proliferation, migration, and gene expression. In vivo tumor growth assays and histological analyses were conducted to assess the role of TET3 in tumor progression. Additionally, we assessed the impact of TET3 on stemness-associated gene expression and performed sphere formation assays to evaluate tumor cell self-renewal capacity. TET3 was highly expressed in tumor-promoting cells. Its knockdown significantly reduced cell proliferation, migration, and tumor growth in vivo. Tumors with TET3 knockdown had lower volumes, weights, and Ki67-positive cells. Mechanistically, TET3 regulated key tumor-related genes and pathways and reduced DNA 5hmC levels. Notably, TET3 knockdown downregulated multiple stemness-related transcription factors such as SOX2 and NANOG, and impaired sphere-forming efficiency, suggesting its essential role in maintaining cancer cell stemness. This study reveals that TET3 promotes tumor growth and progression in bladder cancer partly through modulation of the stemness pathway, highlighting its potential as a therapeutic target and prognostic marker.
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2024
·
IF 7.5
Weigang Wang,Na Yang,Liangliang Wang,Yuanxiang Zhu,Xiao Chu,Weijie Xu,Yawei Li,Yihai Xu,Lina Gao,Beibei Zhang,Guoqiang Zhang,Qinmiao Sun,Weihong Wang,Qiang Wang,Wenxin Zhang,Dahua Chen
Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.
研究领域:
发育生物学
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分子遗传学
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颅面生物学
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产品关联
DOI
PubMed
高影响因子
Cell Metabolism
·
2025
·
IF 30.9
Tiezhu Shi,Jialiang Shao,Yufeng Ding,Hong Tang,Xiangyin Tan,Sisi Zhou,Shaoqing Yu,Xiang Wang,Guanzhen Yu,Ninghan Feng,Xiongjun Wang
Metabolic adaptations involved in tumor metastasis and immune evasion merit investigation. Here, using in vivo metabolic CRISPR/Cas9 knockout screening, we identified xylulokinase (XYLB) as a tumor suppressor that impairs lung colonialization by producing xylulose 5-phosphate (Xu5P), which promotes CD8 + T cell cytotoxicity. Mechanistically, CD8 + T cells express relatively high levels of solute carrier family 35 member E2 (SLC35E2), a homolog of the plant Xu5P transporter, to facilitate Xu5P uptake and subsequently intensify the pentose phosphate pathway and glycolysis for energy/redox balance. Furthermore, we revealed that Xu5P potentiates CD8 + T cell response by promoting Xu5P-responsive progenitor-like SLC35E2 + CD8 + exhausted T cells via tet methylcytosine dioxygenase 3 (TET3)-mediated DNA demethylation of the Tcf7 promoter. Clinically, elevated XYLB or blood Xu5P correlates with enhanced CD8 + T cell efficacy and reduced metastasis. In murine models, Xu5P supplementation or adopting Xu5P-rich diets synergizes with anti-PD-1 therapy to enhance antitumor immunity. These findings offer insights into the potentiality of dietary interventions for metastatic cancer.
研究领域:
癌症生物学
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免疫学
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代谢工程
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分子生物学
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遗传学
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肿瘤免疫学
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营养科学
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细胞信号传导
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DOI
PubMed
高影响因子
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