Heliyon
·
2023
·
IF 4
Hang-fei Chen,Zhang-ping Li,Qi Wu,Chun Yu,Jing-Yi Yan,Yong-feng Bai,Sheng-mei Zhu,Mao-xiang Qian,Ming Liu,Li-feng Xu,Zheng Peng,Feng Zhang
Hyperactivation of ribosome biosynthesis (RiBi) is a hallmark of cancer, and targeting ribosome biogenesis has emerged as a potential therapeutic strategy. The depletion of TAF1B , a major component of selectivity factor 1 ( SL1 ), disrupts the pre-initiation complex, preventing RNA polymerase I from binding ribosomal DNA and inhibiting the hyperactivation of RiBi. Here, we investigate the role of TAF1B , in regulating RiBi and proliferation in stomach adenocarcinoma (STAD). We disclosed that the overexpression of TAF1B correlates with poor prognosis in STAD, and found that knocking down TAF1B effectively inhibits STAD cell proliferation and survival in vitro and in vivo. TAF1B knockdown may also induce nucleolar stress, and promote c-MYC degradation in STAD cells. Furthermore, we demonstrate that TAF1B depletion impairs rRNA gene transcription and processing, leading to reduced ribosome biogenesis. Collectively, our findings suggest that TAF1B may serve as a potential therapeutic target for STAD and highlight the importance of RiBi in cancer progression.
研究领域:
癌症生物学
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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
JOURNAL OF CHEMOTHERAPY
·
2023
·
IF 1.8
Yanzhao Jin,Jiaqing Cao,Hua Cheng,Xiaoyun Hu
This study aimed to investigate the role and mechanism of POU6F2-AS2 in the development of gastric cancer. POU6F2-AS2 expression was considerably higher in clinical stomach adenocarcinoma (STAD) tissues and gastric cancer cell lines (MKN-28 and MGC-803) than in neighbouring normal tissues and gastric mucosa epithelial cells (GES-1). POU6F2-AS2 overexpression resulted in a low overall survival probability, progression-free survival probability and post progression survival probability, as well as increased cell viability, migration and invasion of gastric cancer cells, thereby inhibiting apoptosis. Based on RNA pull-down, cycloheximide and MG132 incubation experiments, POU6F2-AS2 promoted SKP2 by stabilizing NONO expression. In addition, in vivo silencing of POU6F2-AS2 in gastric cancer cells can inhibit tumour progression and produce a synergistic antitumour effect when combined with paclitaxel. POU6F2-AS2 is overexpressed in STAD, which is attributed to a bad prognosis. In vitro and in vivo experiments have confirmed that the POU6F2-AS2/NONO/SKP2 axis promotes STAD progression, and that the silencing of POU6F2-AS2 plays a synergistic antitumour effect when combined with paclitaxel. Therefore, POU6F2-AS2 may be potentially developed as a target to inhibit STAD and reduce chemoresistance.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Dongjian Song,Qiuliang Liu,Zechen Yan,Qi Wang,Meng Su,Hui Zhang,Longyan Shi,Yingzhong Fan,Qian Zhang,Heying Yang,Da Zhang
This study investigates the molecular mechanisms by which superparamagnetic iron oxide nanoparticles (SPIONs) loaded with the WSGC peptide (WSGC@FA@PEG/PEI-SPIONs)—a 40-amino acid polypeptide derived from apoC-III—modulate chemotherapy resistance in gastric adenocarcinoma (GA). Emphasis is placed on their role in regulating mitophagy and mitochondrial homeostasis via the Notch signaling pathway. The physicochemical properties of WSGC@FA@PEG/PEI-SPIONs are thoroughly characterized, demonstrating favorable biocompatibility, stable size distribution, and efficient peptide loading. In vitro experiments show that these nanoparticles significantly inhibit GA cell proliferation, migration, and invasion by downregulating mitophagy-associated proteins (LC3, PINK1, and Parkin), primarily through modulation of the Notch pathway. In vivo studies, using a GA nude mouse model, confirm the therapeutic potential of WSGC@FA@PEG/PEI-SPIONs, revealing marked tumor growth inhibition and increased apoptotic activity. Collectively, the findings highlight the WSGC peptide as a promising therapeutic agent for overcoming chemotherapy resistance in GA by targeting the Notch signaling pathway and suppressing mitophagy, thereby presenting a novel strategy for polypeptide-based cancer therapy.
研究领域:
纳米医学
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肿瘤学
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分子生物学
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药理学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2017
·Vol. 38
·期 6
·3583-3591
·
IF 2.662
Shilei Zang,Qiling Tang,Fangrui Dong,Huan Liu,Lili Li,Fang Guo,Xuediao Pan,Haorong Lin,Weibin Zeng,Zhaoxu Cai,Qibin Zhong,Ning Zang,Linquan Zang
Curcumol, a polyphenol compound derived from the rhizome of Curcuma, has been established as an antitumor compound against multiple types of cancer, including gastric (GC), lung, liver and breast cancer. However, the molecular mechanisms undelying its anticancer activity in GC are still unclear. In this study, the antitumor efficacy of curcumol was ascertained in human gastric adenocarcinoma MGC-803 cells. An MTT assay was used to assess the viability of the MGC-803 cells treated by curcumol. The results of the Annexin V/propidium iodide (PI) staining followed by fluorescence activated cell sorting (FACS) analysis demonstrated that the cell cycle was arrested in the G2/M phase by curcumol. Annexin V-FITC/PI double staining followed by FACS analysis revealed that curcumol induced apoptosis of MGC-803 cells. FACS analysis after the cells were loaded with a DFCH-DA probe revealed that the level of reactive oxygen species (ROS) increased after the cells were treated with curcumol. In adittion, FACS analysis after the cells were loaded with JC-1 revealed that the level of mitochondrial membrane potential (MMP) decreased after the cells were treated with curcumol. Furthermore, the downregulation of isocitrate dehydrogenase 1 (IDH1) was observed in the MGC-803 cells after being treated with curcumol as determined by western blotting and RT-qPCR. In conclusion, we elucidated the antitumor effect of curcumol on MGC-803 cells and the involved mechanisms related to the induction of apoptosis, the increase of ROS, the decrease of MMP and the downregulation of IDH1.
研究领域:
肿瘤学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Oncology
·
2025
·
IF 3.3
Chen Dai,Rishun Su,Zhenzhen Zhao,Yangyang Guo,Wenbin Hou,Yulong He,Guangyao Liu,Songcheng Yin,Changhua Zhang
Background Gastric cancer (GC) is a very aggressive, with extreme heterogeneity and rapid growth, most frequently manifested histologically as stomach adenocarcinoma (STAD). Current evidence suggests that histone acetylation is critical for the origin and development of tumors. However, the significance of histone acetylation-related gene signatures for prognosis of STAD patients and mechanisms of histone acetylation in STAD therapy remains unclear. Methods We identified histone acetylation-related genes in STAD from TCGA and constructed eight-gene signatures by utilizing a univariate Cox regression model with the Least Absolute Shrinkage and Selection Operator (LASSO). In addition, a nomogram was plotted to predict the prognostic significance of the established risk model. We examined associations between our gene signature and somatic mutation, immune subtype, clinicopathological features, tumor microenvironment, immune cell infiltration and immune activity, immunotherapy prediction and drug sensitivity. Cell-based assays were performed to determine the relationship between Doublecortin Like Kinase 1 (DCLK1) and the proliferation, migration and oxaliplatin resistance of GC cells in vitro . Immunohistochemical experiments were used to explore the relationship between DCLK1 and clinicopathological parameters. Results A prognostic model composed of eight histone acetylation-related genes in STAD was developed. Based on median risk score, the STAD patients were equally assigned into two groups of high- and low-risk, where high-risk represented a less favorable prognosis than low-risk. The two groups showed significant differences with respect to somatic mutation, immune subtype, clinicopathological features, tumor microenvironment, immune cell infiltration and immune activity, immunotherapy prediction and drug sensitivity. The results generated during Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that Differentially Expressed Genes (DEGs) in the two groups were involved in cancer-related processes and pathways. Cell-based assays indicated that DCLK1 is a promoting factor in gastric cancer and can promote oxaliplatin resistance in gastric cancer cells. Increased DCLK1 expression was also associated with Borrmann’s Type, depth of invasion, lymph node metastasis, and TNM stage in GC patients. Conclusion A novel histone acetylation-related gene signature, which possesses potential value in predicting the prognosis and immunotherapy effectiveness regarding STAD patients, was developed. This signature may serve as a reliable biomarker for prognosis of STAD and promote the identification of novel treatment targets for STAD. Furthermore, DCLK1 exhibited oncogenic roles and may be a new target for STAD therapy.
研究领域:
肿瘤学
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分子生物学
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免疫治疗
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生物信息学
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癌症基因组学
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产品关联
DOI
PubMed
高影响因子
HUMAN MUTATION
·
2025
·Vol. 2025
·期 1
·5319444
·
IF 3.7
Xin Wu,Linde Sun,Peifa Liu,Qiong Wang,Yu Wang
Background PANoptosis, as an inflammatory programmed cell death, is involved in tumor development. This study set out to discover novel PANoptosis-correlated prognostic signatures in stomach adenocarcinoma (STAD), a prevalent malignancy of the digestive system. Methods STAD samples were derived from a public database, and PANoptosis-related genes (PRGs) were acquired from existing reports. Prognosis-related PRGs were screened by univariate Cox regression analysis. Molecular subtypes of STAD were identified by the “ConsensusClusterPlus” package. The “Limma” package was employed to filter differentially expressed genes (DEGs) between different subtypes. PANoptosis-related prognostic signatures in STAD were identified to establish the RiskScore model. The RiskScore and some of the clinical features were integrated to establish a nomogram. Immune cell infiltration and TIDE score in different risk groups were compared. Correlation between immune checkpoint genes, drug sensitivity, and RiskScore was analyzed by the Spearman method. The biological function of PANoptosis-related signature genes in STAD was preliminarily explored by in vitro cell experiments. Results Based on 18 prognosis-related PRGs, two molecular subtypes of STAD were recognized, and the C1 subtype showed a lower overall survival (OS) rate than the C2 subtype. Further, three PANoptosis-related signature genes ( APOD , GPC3 , and SERPINE1 ) were determined to establish a RiskScore model that could accurately assess the prognostic outcomes for STAD patients. Then, by integrating RiskScore with clinical features, a nomogram was established. The high-risk group had higher immune cell infiltration and TIDE score and lower OS rate than those with a low risk. RiskScore was positively correlated with nine immune checkpoint genes. Besides, we screened 23 drugs that significantly correlated with RiskScore. In vitro cell experiments showed that the mRNA and protein levels of APOD , GPC3 , and SERPINE1 were upregulated in the STAD cell line and that APOD knockout significantly reduced cancer cell proliferation, migration, and invasion levels and increased the apoptotic capacity of the STAD cell line. Conclusion This study established a PANoptosis-related RiskScore model for assessing STAD patient prognosis, which could contribute to the personalized treatment of STAD.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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免疫治疗
·
精准医学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Yao Yao,Yue Zhao,Huijuan Zhang,Wenting Pan,Wei Liang,Yijian Jiang,Xinlong Yan,Yinzhou Yan
The development of surface-enhanced Raman spectroscopy (SERS) as an ultrasensitive fingerprint analysis technique in precision medicine requires high-performance SERS substrates with controllable nanostructure (hot-spot) distribution, simple fabrication, superior stability, biocompatibility, and extraordinary optical responses. Unfortunately, fabrication of arbitrary nanostructures with high homogeneity on a large scale for SERS is still challenging. Herein, we report an ultrafast laser parallel fabrication protocol for Au/2D-transition-metal dichalcogenide hybrid SERS biosensors. The leveraged photonic nanojets (PNJs) are generated by a micron-sized microsphere monolayer to simultaneously trigger localized phase transition in 2H-MoTe2, achieving a 1T′-MoTe2 nanopattern array with a density of 1 million per mm2 by a single laser shot. The Au nanoparticle clusters (AuNCs) are subsequently grown in situ from the 1T′ regions, creating a AuNCs on 1T′/2H-MoTe2 (AuNCs@1T’/2H-MoTe2) hybrid SERS substrate. The fabricated feature diameter and overlay accuracy of the patterned AuNCs are 210.1 ± 3.4 and 9.2 ± 1.7 nm, respectively. To eliminate background noise, we designed dimer-AuNCs@1T′/2H-MoTe2 (dAuNCs@1T′/2H-MoTe2), achieving a detection limit of 10–13 M with an enhancement factor of 4.9 × 108 for the methylene blue (MB) analyte. The strong localized surface plasmon resonances in the dAuNCs as well as efficient charge transfers between Au, 2H-MoTe2, and MB contribute to the majority of Raman enhancement. The multiscale dAuNCs@1T′/2H-MoTe2 array provides a powerful SERSome (comprising multiple SERS spectra) platform for therapeutic drug monitoring, by which we successfully identified the metabolic behaviors of living gastric adenocarcinoma cells administered with two drugs, i.e., capecitabine, oxaliplatin, and their combination. The present work establishes opportunities for creating a highly ordered nanopattern array for ultrasensitive SERSome analysis of cell metabolism in cancer therapy.
研究领域:
纳米技术
·
生物医学工程
·
分析化学
·
癌症研究
·
材料科学
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光学与光子学
·
精准医学
✓ 已验证
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）