International Journal of Medical Sciences
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2025
·Vol. 22
·期 15
·3839-3853
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IF 3.2
Wen Weijia,Li Jiaying,Yuan Li,Liao Yan,Shao Caixia,Xu Dingze,Jiang Hongye,Liao Yuandong,Liu Pan,Zhang Chunyu,Yao Shuzhong,Wang Wei
Lymph node metastasis (LNM) confers significant treatment failure and adverse clinical outcomes in cervical cancer (CCa). However, large unknown lies in the mechanisms underlying LNM in CCa. In this study, we discovered that PRDX3 is elevated in CCa with LNM and associates with poor prognosis in CCa patients. Moreover, multivariate logistic analysis revealed that PRDX3 is an independent predictor of LNM in CCa. Functional investigations demonstrated that PRDX3 promotes invasion, lymphangiogenesis, and LNM of CCa. Mechanistically, PRDX3 activates NF-κB signaling pathway and upregulates the downstream pro-metastatic molecules VEGF-C and MMP-9 in CCa cells. Furthermore, PRDX3 could inhibit the anoikis of detached CCa cells by reducing the ROS level and hence promote LNM in CCa. Importantly, genetic inhibition of PRDX3 potently slows LNM of CCa. These findings highlight a novel PRDX3-mediated mechanism of LNM in CCa and recognize PRDX3 as a promising predictive marker and target of clinical intervention for LNM in CCa.
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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癌症研究
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信号转导
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
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2016
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IF 4.173
Zhilei Liu,Yadong Hu,Haisha Liang,Zhongyuan Sun,Shan Feng,Haiteng Deng
PRDX3 is a mitochondrial peroxide reductase that regulates cellular redox state. It has been reported that PRDX3 is overexpressed in liver cancer, but how PRDX3 is involved in hepatocellular carcinoma (HCC) tumorigenesis and progression has not been well-characterized. In the present study, we established two stable cell lines by overexpressing or knocking down PRDX3 in HepG2 cells. We found that PRDX3 silencing decreased the growth rate of HepG2 cells and increased mtDNA oxidation. Quantitative proteomics identified 475 differentially expressed proteins between the PRDX3 knockdown and the control cells. These proteins were involved in antioxidant activity, angiogenesis, cell adhesion, cell growth, ATP synthesis, nucleic acid binding, redox, and chaperones. PRDX3 knockdown led to the down-regulation of ATP synthases and the decreased cellular ATP level, contributing to the slow-down of cell growth. Furthermore, silencing PRDX3 enhanced invasive properties of HepG2 cells via TIMP-1 down-regulation and the increased ECM degradation. Taken together, our results indicate that PRDX3 promotes HCC growth and mediates cell migration and invasiveness and is a potential therapeutic target for HCC treatment.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2016
·
IF 5.784
Zhilei Liu,Yadong Hu,Yiyi Gong,Wenhao Zhang,Chongdong Liu,Qingtao Wang,Haiteng Deng
Isoform 1 of uracil-DNA glycosylase (UNG1) is the major protein for initiating base-excision repair in mitochondria and is in close proximity to the respiratory chain that generates reactive oxygen species (ROS). Effects of ROS on the stability of UNG1 have not been well characterized. In the present study, we found that overexpression of UNG1 enhanced cells’ resistance to oxidative stress and protected mitochondrial DNA (mtDNA) from oxidation . Proteomics analysis showed that UNG1 bound to eight proteins in the mitochondria, including PAPSS2, CD70 antigen , and AGR2 under normal growth conditions, whereas UNG1 mainly bound to Peroxiredoxin 3 (PRDX3) via a disulfide linkage under oxidative stress. We further demonstrated that the UNG1-PRDX3 interaction protected UNG1 from ROS-mediated degradation and prevented mtDNA oxidation. Moreover, our results show that ROS-mediated UNG1 degradation was Lon protease 1 (LonP1)-dependent and mitochondrial UNG1 degradation was aggravated by knockdown of PRDX3 expression. Taken together, these results reveal a novel function of UNG1 in the recruitment of PRDX3 to mtDNA under oxidative stress, enabling protection of UNG1 and UNG1-bound DNA from ROS damage and enhancing cell resistance to oxidative stress.
研究领域:
分子生物学
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细胞生物学
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生物化学
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遗传学
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DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Hui Ni,Zijia Zhang,Ye Lu,Yaowen Liu,Yang Zhou,Wenyong Wu,Xinqin Kong,Liling Shen,Sihan Chen,Huali Long,Cheng Luo,Hao Zhang,Jinjun Hou,Wanying Wu
The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C 18 column and a conventional C 18 column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, thirteen 2D fractions of Uncaria alkaloids were prepared, and their components were characterized using mass spectrometry. Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the thirteen 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine, corynoxeine N -oxide, and cadambine demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H 2 O 2 measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H 2 O 2 clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.
研究领域:
药理学
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分析化学
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传统医学
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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）