Journal of Translational Medicine
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2024
·Vol. 22
·期 1
·1-19
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IF 6.1
Wang Runze,Xue Wei,Kan Feifei,Zhang Huiying,Wang Di,Wang Lei,Wang Jianwen
Background Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels, which leads to vitreous hemorrhage and retinal traction, thereby significantly impairing patient vision. NSUN2-mediated RNA m 5 C methylation is implicated in various diseases, and in this investigation, we focused on elucidating the impact of NSUN2 on the regulation of the expression of the downstream gene MUC1, specifically through RNA m 5 C methylation, on the progression of DR. Method Utilizing Microarray analysis, we examined patient vitreous fluid to pinpoint potential therapeutic targets for DR. Differential expression of NSUN2 was validated through qRT-PCR, Western blot, and immunofluorescence in human tissue, animal tissue, and cell model of DR. The relationship between NSUN2 and DR was explored in vitro and in vivo through gene knockdown and overexpression. Various techniques, such as MeRIP-qPCR and dot blot, were applied to reveal the downstream targets and mechanism of action of NSUN2. Results The levels of both NSUN2 and RNA m 5 C methylation were significantly elevated in the DR model. Knockdown of NSUN2 mitigated DR lesion formation both in vitro and in vivo. Mechanistically, NSUN2 promoted MUC1 expression by binding to the RNA m 5 C reader ALYREF. Knockdown of ALYREF resulted in DR lesion alterations similar to those observed with NSUN2 knockdown. Moreover, MUC1 overexpression successfully reversed a series of DR alterations induced by NSUN2 silencing. Conclusions NSUN2 regulates the expression of MUC1 through ALYREF-mediated RNA m 5 C methylation, thereby regulating the progression of DR and providing a new option for the treatment of DR in the future.
研究领域:
眼科学
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分子生物学
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表观遗传学
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DOI
高影响因子
Cancer & Metabolism
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2025
·Vol. 13
·期 1
·1-17
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IF 5.3
Li Hao,Gong Tingyue,Zhao Yongheng,Luo Yang,Tang Shuibin,Wang Tingfeng,Lin Haiping,Zhong Ming
Purpose Cancer cells rely on serine biosynthesis for growth, but its regulation in colorectal cancer (CRC) remains not well understood. This study identifies the m 5 C methyltransferase NSUN2 (NOP2/Sun domain family, member 2) as a key regulator of serine biosynthesis, revealing a novel mechanism driving CRC progression. Methods The expression and prognostic value of NSUN2 were evaluated using bioinformatics analyses and immunohistochemistry (IHC) assays. The effects of NSUN2 on cellular serine biosynthesis, intracellular reactive oxygen species (ROS) levels, and apoptosis levels were analyzed both in vitro and in vivo. Additionally, RNA sequencing, Methylated RNA Immunoprecipitation sequencing (MeRIP-seq), RNA immunoprecipitation (RIP), and RNA stability assays were utilized to screen and validate the association between NSUN2 and phosphoglycerate dehydrogenase (PHGDH). Results NSUN2 was found to be highly expressed in CRC and associated with poor patient survival. PHGDH, a direct downstream target of NSUN2, plays a crucial role in NSUN2-mediated serine biosynthesis. Furthermore, inhibition of NSUN2 significantly reduced the intracellular NADH/NAD + and NADPH/NADP + ratios, leading to an increase in ROS levels and apoptosis levels, thereby inhibiting CRC progression. Additionally, NSUN2 enhances PHGDH expression and mRNA stability by binding to the “reader” protein m 5 C-Aly/REF export factor (ALYREF). Conclusions This study identified a novel NSUN2/ALYREF/m 5 C-PHGDH axis might be promising therapeutic targets for CRC.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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RNA生物学
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代谢调控
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产品关联
DOI
PubMed
高影响因子
ACS Omega
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2025
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IF 4.3
Na Feng,Junjie Chang,Honglei Yu,Tongfei Li,Lin Lei,Xiaomin Huang,Dandan Shi,Rui Liu,Wenjun Zhang,Xiju He
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide. Doxorubicin (Dox), a conventional chemotherapeutic agent, exhibits unsatisfactory efficacy in HCC due to its poor tumor response, severe cardiotoxicity, and drug resistance. It is urgent to develop strategies to mitigate the side effects and enhance the chemosensitivity of conventional chemotherapy drugs. Traditional Chinese medicine has gained research interest in cancer treatment due to its homology with food and minimal side effects. Puerarin (Pue) has been identified as an effective inhibitor of tumor cell proliferation. However, puerarin’s poor water solubility and bioavailability limit its pharmaceutical application. In this study, a novel puerarin nanoparticle (nanoPue) was developed to overcome its limitation. NanoPue could significantly inhibit tumor growth and enhance the chemotherapeutic effect of Dox in HCC models. NanoPue could increase the perivascular coverage within the tumors; decrease the expressions of NSUN2, p-AKT, VEGFA, and MMP-9; and reduce endothelial cell tube formation. In summary, nanoPue improves Dox therapeutic efficacy by decreasing angiogenic factors via regulating NSUN2 in HCC. This study may provide a potential avenue for advancing nanoPue to enhance chemotherapeutic agents in HCC therapy and supply a theoretical support for the clinical application of nanoPue.
研究领域:
肿瘤学
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药理学
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纳米技术
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分子生物学
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中医药学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Research
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2025
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IF 9.6
Yunsheng Lu,Yibin Huang,Chenchen Mao,Pengfei Shan,Chenkang Wu,Jiongzhou Zhu,Yujie Lin,Zhongyu Li,Mingdong Lu
Silencing NOP2/Sun RNA methyltransferase family member 2 (NSUN2) effectively inhibits gastric cancer (GC) progression but is limited by RNase degradation, rapid renal clearance, and low uptake. Based on the characteristic high levels of reactive oxygen species (ROS) in the tumor microenvironment, this study designed and synthesized a novel ROS-responsive ferrocene nanoparticle loaded with siNSUN2 (PRPFc@siNSUN2). Under ROS conditions, the nanoparticle disintegrates to release siNSUN2. Characterization by proton nuclear magnetic resonance, transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry revealed that PRPFc@siNSUN2 is spherical, with an average diameter of 88.79 ± 1.14 nm, an encapsulation efficiency of 83.10%, and a drug loading capacity of 13.85%. Moreover, these nanoparticles demonstrated excellent stability and, under hydrogen peroxide conditions, exhibited structural disruption leading to the release of siNSUN2, thereby confirming their high ROS responsiveness. In vitro, PRPFc@siNSUN2 markedly enhanced the inhibition of GC cell proliferation, migration, and invasion, and promoted apoptosis, accompanied by increased intracellular ROS and improved siNSUN2 uptake. In vivo studies further confirmed that PRPFc@siNSUN2 markedly enhanced the therapeutic efficacy of siNSUN2 against GC, while exhibiting low cytotoxicity and good biocompatibility. Overall, our findings indicate that PRPFc@siNSUN2, with its favorable morphology, stability, and ROS-triggered release, substantially improves the anti-GC effects of siNSUN2 by inhibiting GC cell proliferation, migration, and invasion, as well as by promoting apoptosis. These results support NSUN2 as a promising therapeutic target and underscore the potential of PRPFc@siNSUN2 nanoparticles in drug delivery, offering a novel strategy to improve clinical outcomes for GC patients.
研究领域:
肿瘤学
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分子生物学
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药剂学
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DOI
PubMed
高影响因子
Genes
·
2021
·Vol. 12
·期 10
·1488
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IF 4.096
Jizhong Zhao,Hongmei Hu,Sheng Wang,Li Wang,Rui Wang
In living organisms, RNA regulates gene expression, cell migration, differentiation, and cell death. 5-Methylcytosine is a post-transcriptional RNA modification in a wide range of RNA species, including messenger RNAs. The addition of m5C to RNA cytosines is enabled by theNSUNenzyme family, a critical RNA methyltransferase. In this study, natural lysines modified with special groups were synthesized. Through two rounds of positive screening and one round of negative screening, we evaluated and identified theMbPylRS-tRNACUAunnatural lysine substitution system, which specifically recognizes lysine with a defined group. Moreover, non-natural lysine substitution at C271 ofNSUN2active site and the subsequent fluorescent labeling was realized through the click reaction. Then, the function of theNSUN2mutant and its upregulatedCDK1gene as well as its effect on cell proliferation were evaluated. Efficient labeling and regulation ofNSUN2was achieved, laying the basis for further studies on the function and regulatory mechanism of upregulated genes.Keywords:RNA modification;m5C;NSUN enzyme;regulation;labeling
研究领域:
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
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Zhe Du,Qingping Liu,Mengruo Wang,Yifu Gao,Qi Li,Yizhe Yang,Tianyu Lu,Lei Bao,Yaxian Pang,Haijun Wang,Yujie Niu,Rong Zhang
Accumulating evidence indicates that maternal exposure to carbon black nanoparticles (CBNPs) during gestation can induce multiple system abnormalities in offspring, whereas its potential mechanism in respiratory disease is still largely unknown. In order to explore the effect of maternal exposure to CBNPs on offspring’s lung and latent pathogenesis, we respectively established in vivo model of pregnant rats exposed to CBNPs and ex vivo model of lung epithelial cells treated with pups’ serum of pregnant rats exposed to CBNPs. After maternal exposure to CBNPs, epithelial-mesenchymal transition (EMT) and fibrosis levels increased as a result of DDRGK1-mediated reticulophagy upregulated in offspring’s lung. DDRGK1 as FAM134B’s cargo bound with FAM134B to mediate reticulophagy. Transcription factor “SP1” positively regulated DDRGK1 gene expression by binding to its promoter. Furthermore, the upregulation of NSUN2 elevated m 5 C methylation of SP1 mRNA and the protein level of SP1 subsequently increased through Ybx1 recognizing and stabilizing m 5 C-methylated SP1 mRNA, followed by the increased levels of reticulophagy and fibrosis in lung epithelial cells treated with offspring’s serum of matrix exposed to CBNPs during gestation. In conclusion, NSUN2/Ybx1/m 5 C-SP1 axis promoted DDRGK1-mediated reticulophagy, which played an important role in EMT-induced fibrosis in offspring’s lung tissue after maternal exposure to CBNPs during gestation.
研究领域:
呼吸系统疾病
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纳米毒理学
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分子生物学
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表观遗传学
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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）