VETERINARY MICROBIOLOGY
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2025
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IF 2.7
Xiaomei Du,Qi Xiao,Li Yang,Yiyi Shan,Yueqing Hu,Wenbin Bao,Shenglong Wu,Zhengchang Wu
Porcine circovirus type 2 (PCV2) is the main pathogen causing postweaning multisystemic wasting syndrome, which leads to enormous losses for porcine industry. However, the regulatory mechanism of PCV2 replication in host cells remains not been clarified. Here, pig DNMT3B was identified as be a host regulator associated with PCV2 infection via RNA-seq analysis. We demonstrated that upregulation of DNMT3B expression can effectively inhibit PCV2 replication in PK15 cells. Besides, TMEM37 acts as a key downstream target of DNMT3B in PCV2-infected PK15 cells. TMEM37 knockdown significantly slowed Ca 2+ influx, and thus inhibited PCV2 replication. Taken together, DNMT3B is required for the PCV2-based infection regulation in host cells. Our findings indicated that DNMT3B inhibits PCV2 replication via targeting TMEM37 to regulate Ca 2+ influx in PK15 cells, which offering a theoretical foundation for the use of this gene as a key biomarker for breeding strategies seeking to improve porcine disease resistance.
研究领域:
兽医学
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分子生物学
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病毒学
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动物遗传学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
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2026
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IF 4.7
Jiang Ling,Zhang Xiaolin,Dai Meng,Bi Ying,Han Lingling,Tao Xiaofeng,Wang Qi
Metastasis is the leading cause of death in patients with lung adenocarcinoma (LUAD), highlighting the urgent need to identify novel therapeutic targets. GLIS family zinc finger 1 (GLIS1) is a transcription factor implicated in multiple cancers. However, its role in LUAD remains poorly defined. In this study, we first identified that GLIS1 was significantly upregulated in LUAD tissues. To modulate its expression, lentiviral vectors were constructed to knock down or overexpress GLIS1 in NCI-H1975 and A549 LUAD cell lines, respectively. In vitro gain- and loss-of-function experiments revealed that GLIS1 knockdown significantly inhibited the migratory and invasive capabilities of NCI-H1975 cells. Conversely, GLIS1 overexpression enhanced these malignant phenotypes in A549 cells. In vivo study demonstrated that GLIS1 knockdown substantially reduced liver and lung metastasis of NCI-H1975 cells in mice. Furthermore, we found that downregulation of GLIS1 suppressed LUAD cell migration by inhibiting Homeobox A9 (HOXA9) methylation, which led to the subsequent upregulation of HOXA9 expression. Mechanistically, GLIS1 knockdown transcriptionally suppressed the mRNA level of the DNA methyltransferase DNMT3B, thereby attenuating HOXA9 methylation. Specifically, overexpression of DNMT3B led to DNA hypermethylation and transcriptional suppression of HOXA9, thereby partially rescuing the tumor-suppressive effects resulting from GLIS1 knockdown. Our work is the first to implicate the GLIS1/DNMT3B axis in the epigenetic silencing of HOXA9 in LUAD, highlighting the therapeutic potential of targeting GLIS1.
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产品关联
DOI
PubMed
高影响因子
CARDIOVASCULAR DRUGS AND THERAPY
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2026
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IF 3.5
Chen XinJing,Hong Jingxuan
Objective This study aimed to determine whether dexmedetomidine (DEX) attenuates myocardial ischemia/reperfusion injury (MIRI) by regulating DNA methyltransferase 3B (DNMT3B)–mediated methylation of a CpG island within the Kruppel-like factor 4 (KLF4) promoter. Methods A rat model of MIRI was established and treated with DEX, DNMT3B knockdown, or DEX combined with DNMT3B overexpression. Histopathological alterations, apoptosis, and DNMT3B/KLF4 expression were assessed using H&E staining, TUNEL/cTnT co-staining, RT-qPCR, western blot, immunofluorescence, and immunohistochemistry. H9C2 cardiomyocytes subjected to oxygen-glucose deprivation/reperfusion (OGD/R) were treated with DEX and transfected with DNMT3B or KLF4 knockdown/overexpression plasmids. CpG island methylation within the KLF4 promoter was predicted using MSP and ChIP-PCR. Results MIRI impaired cardiac function, increased infarct size and myocardial enzyme release, upregulated DNMT3B expression, downregulated KLF4 expression, and promoted cardiomyocyte apoptosis. DNMT3B was predominantly localized in cTnT-positive cardiomyocytes. DEX treatment or DNMT3B knockdown reduced DNMT3B expression, restored KLF4 levels, and alleviated myocardial injury in vivo as well as OGD/R-induced damage in vitro . DEX was associated with decreased methylation of the investigated CpG island within the KLF4 promoter. DEX may inhibit DNMT3B-mediated promoter hypermethylation, thereby enhancing KLF4 transcription. KLF4 knockdown abolished the cardioprotective effects of DEX, while DNMT3B overexpression reversed DEX-mediated improvements in vivo . Conclusions DEX may attenuate MI/RI by downregulating DNMT3B and reducing methylation at a CpG island within the KLF4 promoter, thereby promoting KLF4 expression. However, the intrinsic resolution limitations of MSP and ChIP-PCR restrict precise mapping of methylation sites. Higher-resolution techniques, such as whole-genome bisulfite sequencing or single-molecule methylation sequencing, are warranted to validate these findings.
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DOI
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
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2024
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IF 3.3
Mangmang Feng,Xiaxia Fan,Jiangying Shi,Shuhua Shan,Songtao Li,Shuiling He,Man Ding,Zhuoyu Li
BACKGROUND Quinoa contains far more nutrients than any traditional grain crop. It is known that terpenoids in quinoa have anti-inflammatory and antitumor effects, but their role in reversing drug resistance remains unclear. RESULTS Our previous studies showed that quinoa-derived terpenoid compounds (QBT) can inhibit the occurrence and development of colon cancer. This study further indicates that QBT markedly reverse drug resistance of colon cancer. The results showed that QBT combined with 5-fluorouracil (5-Fu) treatment significantly enhanced the chemotherapy sensitivity of HCT-8/Fu, compared with 5-Fu treatment alone. Moreover, we found that QBT significantly reduced the expression of drug-resistant proteins (P-gp, MRP1, BCRP), and increased the accumulation of chemotherapy drugs. Taking P-gp as the target for biogenesis prediction analysis, results showed that upregulation of miR-495-3p enhanced the chemosensitivity of drug-resistant HCT-8/Fu cells. Besides, the results showed that miR-495-3p was abnormally methylated in HCT-8/Fu compared with HCT-8 colon cancer cells. The expression of methyltransferases DNMT1, DNMT3a and DNMT3b was abnormal. After QBT treatment, the expression level of methyltransferases returned to normal. In addition, the QBT + 5Fu group showed inhibition of tumors in nude mice. CONCLUSION QBT treatment downregulated the expression of drug-resistant protein P-gp by inhibiting the methylation of miR-495-3p, and enhanced the accumulation of 5-Fu in vivo , which in turn reversed its chemoresistance. This suggests that QBT has potential ability as a new drug-resistance reversal agent in colorectal cancer. © 2024 Society of Chemical Industry.
研究领域:
癌症生物学
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药理学
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分子生物学
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营养科学
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产品关联
DOI
PubMed
高影响因子
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
✓ 已验证
DOI
PubMed
高影响因子
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