COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
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2024
·Vol. 27
·期 13
·1919-1929
·
IF 1.6
Zhang Fei,Chu Mingliang,Liu Jiemin,Zhao Qi,Zhu Yanqiu,Wu Xuefang
Aim: The study aimed to study the potential roles and mechanisms of shikonin in gastric cancer by network pharmacology and biological experiments. Methods: The key genes and targets of shikonin in gastric cancer were predicted by network pharmacology and molecular docking study.
The effect of shikonin on the proliferation, migration, and invasion of gastric cancer cells was detected by the CCK8 method, and wound healing and transwell assays. The expression levels of c-Myc and Yap-1 were detected via western blotting in gastric cancer cells after shikonin intervention.
Results: The results of network pharmacology revealed the key target genes of shikonin on gastric cancer cells to be c-Myc, Yap-1, AKT1, etc. GO and KEGG analysis showed regulation of cell migration, proliferation, adhesion, and other biological processes, including the PI3K-Akt signaling
pathway, HIF-1 signaling pathway, necroptosis, and other cancer pathways. Molecular docking showed shikonin to be most closely combined with protooncogenes c-Myc and Yap-1. In vitro experiments showed that the proliferation rate, migration, and invasion ability of the gastric cancer cell group
decreased significantly after shikonin intervention for 24h. The expression levels of c-Myc and Yap-1 in gastric cancer cells were found to be significantly decreased after shikonin intervention. Conclusion: This study showed protooncogenes c-Myc and Yap-1 to be the core target genes
of shikonin on gastric cancer cells. Shikonin may suppress gastric cancer cells by inhibiting the protooncogenes c-Myc and Yap-1. This suggests that shikonin may be a good candidate for the treatment of gastric cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Turkish Journal of Gastroenterology
·
2025
·Vol. 36
·期 9
·573
·
IF 1.6
Hailiang Liu,Xile Wei,Ye Nie,Jianshan Liu,Ming Fan
Background/Aims: The function and mechanism of ubiquitin-specific protease 34 (USP34) in hepatocellular carcinoma (HCC) were explored to provide new molecular targets for treating HCC. Materials and Methods: In the present study, bioinformatics techniques, quantitative real-time polymerase chain reaction, and western blot were used to detect the level of USP34 in HCC tissues and cell lines. Small interfering RNA of USP34 was transfected into HCC cells, and then Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and transwell assay were performed to verify the proliferation, migration and invasion of HCC cells. Enzyme-linked immunosorbent assay was utilized to assess the glycolysis level in HCC cells. Co-immunoprecipitation was used to evaluate the ubiquitination level of cellular Myc (c-Myc). Results: The expression of USP34 was upregulated in HCC patients and strongly associated with worse outcomes. Meanwhile, interference with USP34 suppressed the proliferation, migration, and invasion of HCC cells. In addition, silencing of USP34 reduced the glucose uptake, lactate production and ATP content in HCC cells, as well as downregulated the expression levels of glycolysis-related proteins (hexokinase 2, glucose transporter 1, pyruvate kinase M2, and lactate dehydrogenase A). Furthermore, the knockdown of USP34 enhanced the ubiquitination level of c-Myc and increased the degradation of c-Myc. Overexpression of c-Myc reverted the inhibitory effects of si-USP34 on the malignant biological behavior in HCC cells. Conclusion: TheUSP34 regulates aerobic glycolysis and inhibits the progression of HCC by accelerating c-Myc ubiquitinated degradation.
研究领域:
肿瘤学
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分子生物学
·
肝胆疾病
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信号转导
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癌症代谢
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DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 4
·1529
·
IF 4.6
Zhixiang Wang,Wentao Liu,Guohu Li,Jiacheng Wang,Bin Zhao,Peishan Huang,Wenjie Mei
Herein, two novel ruthenium(II) complexes coupled by erianinviaa flexible carbon chain, [Ru(phen)2(L1-(CH2)4-erianin)](ClO4)2(L1= 2-(2-(tri-fluoromethyphenyl))-imidazo [4,5f][1–10]phenanthroline (1) and [Ru(phen)2(L2-(CH2)4-eria)](ClO4)2(L2= 2-(4-(tri-fluoromethyphenyl))-imidazo [4,5f][1,10]phenanthroline (2), have been synthesized and investigated as a potential G-quadruplex(G4) DNA stabilizer. Both complexes, especially 2, can bind toc-mycG4 DNA with high affinity by electronic spectra, and the binding constant calculated for 1 and 2 is about 15.1 and 2.05 × 107M−1, respectively. This was further confirmed by the increase in fluorescence intensity for both complexes. Moreover, the positive band at 265 nm in the CD spectra ofc-mycG4 DNA decreased treated with 2, indicating that 2 may bind toc-mycG4 DNA through extern groove binding mode. Furthermore, fluorescence resonance energy transfer (FRET) assay indicated that the melting point ofc-mycG4 DNA treated with 1 and 2 increased 15.5 and 16.5 °C, respectively. Finally, molecular docking showed that 1 can bind toc-mycG4 DNA in the extern groove formed by base pairs G7–G9 and G22–A24, and 2 inserts into the small groove ofc-mycG4 DNA formed by base pairs T19–A24. In summary, these ruthenium(II) complexes, especially 2, can be developed as potentialc-mycG4 DNA stabilizers and will be exploited as potential anticancer agents in the future.Keywords:ruthenium(II) complexes;erianin;c-mycG-quadruplex DNA;stabilizer
研究领域:
生物化学
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药物化学
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DOI
PubMed
高影响因子
Journal of Advanced Research
·
2025
·
IF 13
Yajing Li,Runping Liu,Jianan Li,Feng Gao,Zhi Ma,Kaihong Xie,Fanghong Li,Bing Xu,Qi Zheng,Yajie Cai,Jiaorong Qu,Xiaoyong Xue,Kexin Jia,Xiaojiaoyang Li
Introduction Cholestatic liver diseases are highly prevalent and lack effective treatment, ultimately progressing to end-stage liver diseases. Our recent study indicates that the interplay between c-MYC and lncRNA H19 exacerbates the ductular reaction during cholestasis. Objective: This study aims to unveil the underlying mechanisms of the protective effects of senkyunolide A (SenA) on cholangiocyte overproliferation in cholestatic liver diseases. Methods : Through comprehensive characterization using RNA sequencing, CHIP analysis, protein truncation, amino acid mutation or deletion, and the development of SenA derivatives, we explored the effects and mechanisms of SenA in vivo in bile duct ligation mice and in vitro in primary cholangiocytes. Results : We demonstrated that SenA effectively mitigates cholangiocyte hyperproliferation by epigenetically suppressing c-MYC expression and disrupting the downstream H19, Let-7a and Lin28a. Mechanically, we identified a potential interaction between the carbonyl group in SenA and Arg483 in TRAF6, disrupting the TRAF6-HDAC3 complex. This dissociation facilitates the binding of HDAC3 to the MYC promoter region, resulting in enhanced histone deacetylation and transcriptional suppression. Conclusion : We highlight the therapeutic potential of SenA in cholestatic liver diseases by elucidating its role in epigenetic regulation.
研究领域:
医学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
GENE
·
2022
·
IF 3.913
Defeng Zhao,Gaoyu Hu,Ran Chen,Guoqiang Xiao,Shuangshuang Teng
Cadmium (Cd) pollution threatens the cultivation of the blood clam Tegillarca granosa ( T. granosa ) in coastal regions of the East China Sea. The molecular mechanisms regulating Cd stress response and detoxification in blood clams are largely unclear. In the present study, the full-length T. granosa c-Myc (Tgc-Myc) cDNA was cloned for the first time. The 3063-bp cDNA consisted of a 129-bp 5′ untranslated region (UTR), a 1746-bp 3′ UTR, and a 1188-bp open reading frame encoding a predicted protein of 395 amino acid residues. The predicted protein had a calculated molecular weight of 44.9 kDa and an estimated isoelectric point of 6.82. The predicted protein contained an N-terminal transactivation domain and a C-terminal basic helix-loop-helix leucine zipper domain, which are conserved functional domains of c-Myc proteins. Tgc-Myc showed broad tissue distribution in blood clams, with the highest expression detected in the gill and hepatopancreas. Exposure to Cd, a major heavy metal pollutant in coastal regions of the East China Sea, induced Tgc-Myc expression in gill tissues. Tgc-Myc knockdown led to reduced expression of a variety of stress response/detoxification genes in blood clams cultivated in Cd-contaminated seawater. Tgc-Myc knockdown also led to decreased expression of IGF1R , a proto-oncogene that promotes cell proliferation. These findings indicated that Tgc-Myc regulates Cd-induced stress response and detoxification in blood clams. The upregulation of Tgc-Myc may serve as an approach to generate strains with an enhanced detoxification response and consequently a low heavy metal buildup.
研究领域:
分子生物学
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环境毒理学
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海洋生物学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Xiaoxiang Mo,Xiaoju Shen,Xiaocheng Mo,Fei Yu,Weidan Tan,Zhihua Deng,Jingchuan He,Zhuo Luo,Zhiquan Chen,Jie Yang
Small cell lung cancer (SCLC) is the most malignant lung cancer with rapid growth and early metastasis, but still lacks effective targeted therapies to improve the prognosis. Here, we demonstrated that a novel oncogenic protein, cell migration inducing hyaluronic binding protein (CEMIP), was robustly overexpressed in SCLC tissues than that in noncancerous tissues and high expression of CEMIP predicted poor outcomes in clinical specimens and in large sample size cohorts from public databases (GEPIA 2 and CPTAC). Liquid chromatography mass spectrometry (LC-MS) and in vitro/in vivo functional assays indicated that CEMIP contributed to the proliferation by increasing glutamine consumption and their metabolites (glutamate and glutathione) levels in SCLC cells. Moreover, the addition of a GLS1 inhibitor CB-839 dramatically reduced CEMIP-induced SCLC cell proliferation . Mechanistically, beyond as a scaffold protein , CEMIP facilitates glutamine-dependent cell proliferation through inhibiting c-Myc ubiquitination and increasing c-Myc stabilization and nuclear accumulation via hindering the interaction between FBXW7 (a E3 ubiquitin ligase) and its target substrate c-Myc. Taken together, our findings reveal a novel oncogenic role of CEMIP in sustaining SCLC growth via FBXW7/c-Myc-dependent axis, and provide new evidence that inhibition of CEMIP might be a potential therapeutic strategy for the treatment of SCLC.
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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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Tianwen Liu,Wei Yuan,Mengyao Si,Xiaoning Wang,Xiangping Liu,Xiaoying Wang
The concentration fluctuations of cellular-myelocytomatosis oncogene (c-Myc) protein may be related to a variety of tumors such as lymphoma, therefore, detection of abnormal trace-level changes is of great significance for early predictions. Conventional detection methods suffer from time-consuming analytical processes and insufficient sensitivity. Thus, the development of a sensitive detection method for c-Myc protein in blood is particularly crucial. We developed an electrochemical sensor for the sensitive detection of c-Myc protein based on gold–palladium alloy nanoparticles (AuPd NPs), leveraging its dual-function for both electrode modification and signal tag. Specifically, AuPd NPs were rapidly formed on the electrode surface by electrodeposition techniques to anchor the capture antibodies (Ab I ), which can increase the conductivity and load capacity of the electrode. Subsequently, using toluidine blue (TB) as a reducing agent, TB-AuPd was synthesized in one step, and further utilized to anchor the detection antibodies (Ab II ), which improved the load quantity and electrocatalytic activity of TB. When the target was present, the sandwich sensor was successfully constructed, benefiting from dual amplifications to achieve sensitive detection of c-Myc protein. Eventually, the proposed sensor exhibited a wider linear range (1–1000 pg mL −1 ) and a lower detection limit (0.5 pg mL −1 , S/N = 3). The developed method demonstrated strong concordance with commercially available ELISA kits, with no statistically significant difference observed in detection results. Thus, the proposed sensor realized sensitive detection of c-Myc protein, and can render valuable guidance for prospective clinical test applications.
研究领域:
生物医学工程
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肿瘤学
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分析化学
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产品关联
DOI
高影响因子
JOURNAL OF PHYSICAL CHEMISTRY B
·
2023
·
IF 3.3
Wen Wu,Xia Hu,Zhen Zeng,Di Wu,Hanmei Li,Hui Li
Sorafenib (Sor) is a multitarget kinase inhibitor used clinically to treat hepatocellular carcinoma and renal cancer. In this study, the interaction mechanism of Sor with c-MYC G-quadruplexes (G4) was investigated at the molecular level by computer-aided means and experiments. Molecular docking results predicted the binding of Sor to the groove of G4. Molecular dynamics (MD) simulations were used to evaluate the effect of ligand binding to G4. Ultraviolet (UV), fluorescence spectroscopy, and viscosity experiments showed that the binding site was in the groove. The UV and fluorescence titration results showed that compared with traditional G4 ligands represented by compound meso-tetra (N-methyl-4-pyridyl) porphine (TmPyP4), Sor has a lower affinity for G4. Likewise, results from fluorescence resonance energy transfer (FRET) experiments suggested that Sor could have a limited ability to stabilize G4, but it was not as prominent as that of TmPyP4. Time-resolved fluorescence spectroscopy again supported the results from steady-state fluorescence spectroscopy, indicating that a static quenching mechanism mainly drove the process. Studying the interaction mechanism of Sor and c-MYC may inspire the screening of new, selective c-MYC G4 ligands and provide ideas for the design of drugs with good stability, low toxicity, and specific targeting of G4.
研究领域:
生物化学
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药物化学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
·
2020
·Vol. 106
·期 2
·526-538
·
IF 5.399
Wu Ying-Ting,Ma Si-Yu,Sun Wen-Qin,Shen Wei-Wei,Zhu Hui-Ting,Zhang Qin,Chen Hui-Fen
BackgroundEndometriosis (EM) is a benign gynecological disease that shares some characteristics with malignancy, such as proliferation and invasion. So far, the pathogenesis of EM is still unclear. In this study, we investigated whether TRIM65 can play a role in the development of EM.MethodsTRIM65 expression levels in eutopic, ectopic, and normal endometrium were detected by quantitative real-time PCR and Western blot. Cell proliferation and invasion of primary endometrial stromal (EMS) cells were detected by CCK-8 and Transwell analysis. The interaction between TRIM65 and DUSP6 or C-myc was measured by coimmunoprecipitation, ubiquitylation, dual luciferase, and chromatin immunoprecipitation analysis.ResultsWe found that TRIM65 was identified as an up-regulated gene in ectopic endometrial tissues and EMS cells compared with control groups without EM. TRIM65 expression was positively correlated with the levels of p-ERK1/2, C-myc, matrix metalloproteinase-2, and integrin β1 in ectopic endometrial tissues in patients and mice. TRIM65 promoted the cell proliferation and invasion of EMS cells via the ERK1/2/C-myc pathway through ubiquitination of DUSP6. C-myc promoted TRIM65 expression through inducing TRIM65 promoter activity. Additionally, the increased expression of TRIM65, C-myc, matrix metalloproteinase-2, integrin β1, and p-ERK1/2 and the decreased expression of DUSP6 in ectopic endometrial tissues were significantly suppressed by inhibition of ERK1/2 signaling pathway in ectopic endometrial tissues in experimental mice model.ConclusionIn conclusion, TRIM65 promotes invasion of ectopic EMS cells by activating a feedback loop with the ERK1/2/C-myc signaling pathway and may be a potential therapeutic target for EM.
研究领域:
妇科学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Yijing Kuang,Wei Yuan,Xuyuan Chen,Xiaoning Wang,Xiaoying Wang
Background The expression of oncoprotein c-Myc (OP c-Myc ) in blood is closely related to the occurrence and development of various tumors. Common detection methods have the disadvantages of complicated procedures, expensive instruments, or low sensitivity. Currently, several single-mode immunosensors have been developed to detect OP c-Myc and overcome the above shortcomings. However, they are susceptible to the interference of the sensing interface and the external environment, which may lead to false-positive or false-negative results. Therefore, sensitive and accurate assessment of OP c-Myc levels in the blood is very important for the early diagnosis and monitoring of tumors. Results A novel electrochemiluminescence (ECL)-electrochemical (EC) dual-mode immunosensor was developed for the sensitive detection of trace OP c-Myc . Gold nanoparticles-magnetic reduced graphene oxide (AuMrGO), with a large surface area and conductivity, were stably fixed on a magnetic glassy carbon electrode and utilized as the immobilization platform. Ruthenium(II)tris(bipyridine) (Ru) doped Au, Ag, and Pd trimetallic nanocomposite (Tri-Ru) with excellent ECL and EC properties was synthesized by mechanical alloying method and used as the bifunctional signaling label. Further, combined with the trace detection advantages of indirect competition, the convenient and sensitive dual-mode detection of OP c-Myc was realized. The results showed a strong linear relationship for concentrations from 10 pg L −1 to 0.1 μg L −1 in ECL mode and from 0.1 ng L −1 to 1 μg L −1 in EC mode, with limits of detection (LOD) of 4.9 pg L −1 and 30 pg L −1 , respectively. The assay performed good analytical performances and clinical practicability in lymphoma patients’ blood samples. Significance This is the first detection of OP c-Myc using an ECL immunosensor, and it is also the first attempt to use a dual-mode detection strategy for OP c-Myc . The strategy could be used for sensing and detecting other proteomic tumor markers and established a promising platform for early auxiliary diagnosis and monitoring of cancers.
研究领域:
生物医学工程
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分析化学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Nutrients
·
2022
·Vol. 14
·期 15
·3042
·
IF 6.706
Jun Chen,Zhiguang Duan,Yannan Liu,Rongzhan Fu,Chenhui Zhu
The metastasis of esophageal squamous cell carcinoma (ESCC) is a leading cause of death worldwide, however, it has a poor prognosis. Ginsenoside Rh4 is a rare saponin that has been shown to have potential antitumor effectiveness in ESCC. However, the utility of Rh4 in ESCC metastasis and its undiscovered mode of action has not yet been explored. In this study, we found that Rh4 could inhibit ESCC metastasis by regulating the Wnt/β-catenin signaling pathway and the level of c-Myc, which is an important transcription factor in cancer. In in vitro experiments, Rh4 could inhibit the migration and invasion of ESCC cells without affecting cell viability. In in vivo experiments, Rh4 restrained ESCC metastasis to the lymph nodes and lungs via the suppression of epithelial-mesenchymal transition (EMT). The Wnt agonist HLY78 promoted EMT and migration of ESCC cells, whereas treatment of Rh4 can attenuate the promotion effect of HLY78. The siRNA knocking out c-Myc can also significantly reduce the expression of EMT-related marker proteins. This study illustrates a new concept for further research on the mechanism of Rh4 in ESCC.Keywords:metastasis;ginsenoside Rh4;ESCC;Wnt/β-catenin;c-Myc
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
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
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