Frontiers in Microbiology
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2019
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IF 4.259
Xue Biyun,Hou Gaopeng,Zhang Guixi,Huang Jingjing,Li Liangliang,Nan Yuchen,Mu Yang,Wang Lizhen,Zhang Lu,Han Ximeng,Ren Xiaolei,Zhao Qin,Wu Chunyan,Wang Jingfei,Zhou En-Min
Prevention and control of infection by porcine reproductive and respiratory syndrome virus (PRRSV) remains a challenge, due to our limited understanding of the PRRSV invasion mechanism. Our previous study has shown that PRRSV glycoprotein GP5 interacts with MYH9 C-terminal domain protein (PRA). Here we defined that the first ectodomain of GP5 (GP5-ecto-1) directly interacted with PRA and this interaction triggered PRA and endogenous MYH9 to form filament assembly. More importantly, MYH9 filament assembly was also formed in GP5-ecto-1-transfected MARC-145 cells. Notably, PRRSV infection of MARC-145 cells and porcine alveolar macrophages also induced endogenous MYH9 aggregation and polymerization that were required for subsequent PRRSV internalization. Moreover, overexpression of S100A4, a MYH9-specific disassembly inducer, in MARC-145 cells significantly resulted in diminished MYH9 aggregation and marked inhibition of subsequent virion internalization and infection by both PRRSV-1 and PRRSV-2 isolates. The collective results of this work reveal a novel molecular mechanism employed by MYH9 that helps PRRSV gain entry into permissive cells.
研究领域:
病毒学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Clinical Oncology
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2026
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IF 3
Zhang Peng,Chang Yuan,Yang Xiaolu,He Binglu,Ma Li
Background Breast cancer (BC) represents one of the leading causes of cancer-related mortality in women worldwide. Betulinic acid (BA), a naturally derived pentacyclic triterpenoid, exhibits anti-BC activity. Recent evidence implicates RNF125 , a RING-domain E3 ubiquitin ligase, as a tumor suppressor. This study aimed to elucidate whether BA exerts anti-BC effects via RNF125 regulation and explored the underlying mechanisms. Methods RNF125 -overexpressing or knockdown BC cell lines were generated to examine the regulatory effect on cell proliferation, motility, and invasiveness. Furthermore, a subcutaneous xenograft mouse model was established to evaluate the influence of RNF125 on tumor growth in vivo. Results Bioinformatics analyses revealed BA-mediated upregulation of RNF125 in BC cells. Pan-cancer data indicated reduced RNF125 expression in BC specimens, correlating with unfavorable survival outcomes. Consistently, our results showed that BA upregulates RNF125 protein expression in a concentration-dependent manner. In clinically collected BC samples, diminished RNF125 expression was significantly associated with advanced TNM staging. Functional assays demonstrated that RNF125 overexpression suppressed cell proliferation, migration, and invasion. Conversely, RNF125 knockdown reversed these effects and abrogated BA-mediated suppression of malignant phenotypes in BC cells. Mechanistically, RNF125 interacted with MYH9 (Myosin Heavy Chain 9) to facilitate its ubiquitin-mediated proteasomal degradation. In BA-treated BC cells, the protein expression of MYH9 was inhibited. Ectopic MYH9 expression reversed the tumor-suppressive effects of RNF125 overexpression. Finally, a murine xenograft model confirmed that RNF125 overexpression inhibits BC tumor growth. Conclusion These findings suggested that RNF125 mediates the anti-tumor effect of BA, at least in part, through ubiquitin-dependent degradation of MYH9 . Graphical abstract The alternative text for this image may have been generated using AI.
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2019
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IF 3.743
Xue Li,Hao Liu,Wenqian Yu,Xiaomei Liu,Caixia Liu
Objective Congenital diaphragmatic hernia (CDH) is a common and often lethal birth defect characterized by congenital lung malformation, which severely affects neonate prognosis and mortality. This study aimed to investigate differences in protein expression in order to elucidate the mechanism of CDH-associated pulmonary hypoplasia during the early stage of lung development using tandem mass tag (TMT) quantitative proteomics. Methods Nitrofen was administered orally to establish a rat CDH model, and pathological changes were evaluated through hematoxylin-eosin (H&E), PCNA, and Ki67 staining at the pseudoglandular stage. Fetal lungs were then collected, pooled before TMT labeling, and subjected to mass spectrometry. Immunohistochemistry (IHC), Western blotting, and Q-PCR were used to further validate the candidate proteins. Results A total of 79 differentially expressed proteins (DEPs) were identified when CDH and control lungs were compared, and further bioinformatics analysis showed that these proteins play important roles in tight-junctions, phospholipase D signaling, and the HIF-1 signaling pathway. Three differentially expressed proteins, Cldn3, Magi1, and Myh9 are involved in the tight-junction pathway (P < 0.05), and their differential expressions were confirmed by IHC, Western blotting, and Q-PCR. Conclusion These findings indicate that alterations of tight-junction protein expression may play an important role in the pathogenesis of abnormal lung development in CDH. Further studies are warranted to verify the mechanism by which these tight-junction proteins influence the pathogenesis of CDH-associated pulmonary hypoplasia.
研究领域:
发育生物学
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蛋白质组学
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儿科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 29
·2201541
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IF 17.521
Jiawei Huo,Jie Li,Yang Liu,Libin Yang,Xinran Cao,Chong Zhao,Yicheng Lu,Wei Zhou,Shumu Li,Jianan Liu,Jiao Li,Xing Li,Jing Wan,Rui Wen,Mingming Zhen,Chunru Wang,Chunli Bai
Malignant proliferation and metastasis are the hallmarks of cancer cells. Aminated [70]fullerene exhibits notable antineoplastic effects, promoting it a candidate for multi-targeted cancer drugs. It is an urgent need to reveal the structure–activity relationship for antineoplastic aminated fullerenes. Herein, three amphiphilic derivatives of [60]fullerene with clarified molecular structures are synthesized: TAPC-4, TAPC-3, and TCPC-4. TAPC-4 inhibits the proliferation of diverse tumor cells via G0/G1 cell cycle arrest, reverses the epithelial–mesenchymal transition, and abrogates the high mobility of tumor cells. TAPC-4 can be excreted from the organism and achieves an in vivo inhibition index of 75.5% in tumor proliferation and 87.5% in metastatic melanoma with a wide safety margin. Molecular dynamics simulations reveal that the amphiphilic molecular structure and the ending amino groups promote the targeting of TAPC-4 to heat shock protein Hsp90-beta, vimentin, and myosin heavy chain 9 (MYH9), probably resulting in the alteration of cyclin D1 translation, vimentin expression, and MYH9 location, respectively. This work initially emphasizes the dominant role of the amphiphilic structure and the terminal amino moieties in the antineoplastic effects of aminated fullerenes, providing fundamental support for their anti-tumor drug development.
研究领域:
肿瘤学
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药物化学
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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
Frontiers in Immunology
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2023
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IF 7.3
Qingqing Cao,Haiyan Zhu,Wei Xu,Rongrong Zhang,Yun Wang,Zhaofang Tian,Yufang Yuan
Objective Primary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder among children. While glucocorticoids are the primary first-line treatment for ITP treatment, they prove ineffective in certain patients. The challenge of identifying biomarkers capable of early prediction regarding the response to glucocorticoid therapy in ITP persists. This study aimed to identify ideal biomarkers for predicting glucocorticoid efficacy in patients with ITP using plasma proteomics. Methods A four-dimensional data-independent acquisition approach was performed to determine the differentially expressed proteins in plasma samples collected from glucocorticoid-sensitive (GCS) (n=18) and glucocorticoid-resistant (GCR) (n=17) children with ITP treated with prednisone. The significantly differentially expressed proteins were selected for enzyme-linked immunosorbent assay validation in a cohort conprising 65 samples(30 healthy controls, 18 GCS and 17 GCR children with ITP). Receiver operating characteristics curves, calibration curves, and clinical decision curve analysis were used to determine the diagnostic efficacy of this method. Results 47 differentially expressed proteins (36 up-regulated and 11 down-regulated) were identified in the GCR group compared with the GCS group. The significantly differentially expressed proteins myosin heavy chain 9 (MYH9) and fetuin B (FETUB) were selected for enzyme-linked immunosorbent assay validation. The validation results were consistent with the proteomics analyses. Compared with the GCS group, the GCR group exhibited a significantly reduced the plasma concentration of MYH9 and elevated the plasma concentration of FETUB. Furthermore, the receiver operating characteristics curves, calibration curves, and clinical decision curve analysis demonstrated good diagnostic efficacy of these validated biomarkers. Conclusion This study contributes to the establishment of objective biological indicators for precision therapy in children with ITP. More importantly, the proteins MYH9 and FETUB hold potential as a foundation for making informed decisions regarding alternative treatments for drugresistant patients, thereby preventing treatment delays.
研究领域:
血液学
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蛋白质组学
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儿科
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免疫学
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药理学
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DOI
PubMed
高影响因子
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