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  • Open Access

    ARTICLE

    The Epstein-Barr virus-miRNA-BART6-5p regulates TGF-β/SMAD4 pathway to induce glycolysis and enhance proliferation and metastasis of gastric cancer cells

    XUHUI ZHAO1,2, XIAOMIN HUANG1, CHUNYAN DANG2, XIA WANG1, YUJIAO QI3, HONGLING LI2,*

    Oncology Research, Vol.32, No.5, pp. 999-1009, 2024, DOI:10.32604/or.2024.046679

    Abstract Background: EBV-miR-BARTs exhibit significant relevance in epithelial tumors, particularly in EBV-associated gastric and nasopharyngeal cancers. However, their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored. Material and Methods: Initially, EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines. Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45, and downregulation in EBV-positive cells (SUN-719). The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation, migration, and glycolytic processes, with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-β inhibitor. Results: EBV-miRNA-BART6-5p exhibits pronounced upregulation… More >

  • Open Access

    ARTICLE

    Valtrate exerts anticancer effects on gastric cancer AGS cells by regulating reactive oxygen species-mediated signaling pathways

    JINGLONG CAO1,#, SHUMEI LI2,#, TONG ZHANG1,#, JIAN LIU1, WENSHUANG HOU1, ANQI WANG1, CHANG WANG3,4,*, CHENGHAO JIN1,3,5,*

    BIOCELL, Vol.48, No.2, pp. 313-325, 2024, DOI:10.32604/biocell.2023.043474

    Abstract Background: Valtrate (Val) was extracted from the Valeriana jatamansi Jones plant, had good antitumor activity. However, its precise molecular mechanism in cancer cells was still unclear. This study investigated the effect of Val on gastric cancer (GC) cells and its potential molecular mechanism. Methods: Cell viability was examined by CCK-8 assay. Cell cycle, apoptosis, and Reactive oxygen species (ROS) level were analyzed by flow cytometry. The migration effect of Val on AGS cells was analyzed by transwell and wound-healing assay. The expression levels of proteins were analyzed by western blot. Results: The cell viability assay results demonstrated that Val significantly… More > Graphic Abstract

    Valtrate exerts anticancer effects on gastric cancer AGS cells by regulating reactive oxygen species-mediated signaling pathways

  • Open Access

    ARTICLE

    Gastric cancer secreted miR-214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells

    WEIXUE WANG#, TONGTONG WANG#, YAN ZHANG, TING DENG, HAIYANG ZHANG*, YI BA*

    Oncology Research, Vol.32, No.3, pp. 489-502, 2024, DOI:10.32604/or.2023.046676

    Abstract Different from necrosis, apoptosis, autophagy and other forms of cell death, ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated fatty acids under the action of iron divalent or lipoxygenase, leading to cell death. Apatinib is currently used in the third-line standard treatment of advanced gastric cancer, targeting the anti-angiogenesis pathway. However, Apatinib-mediated ferroptosis in vascular endothelial cells has not been reported yet. Tumor-secreted exosomes can be taken up into target cells to regulate tumor development, but the mechanism related to vascular endothelial cell ferroptosis has not yet been discovered. Here, we show that exosomes secreted by gastric cancer… More >

  • Open Access

    ARTICLE

    NAD+ associated genes as potential biomarkers for predicting the prognosis of gastric cancer

    XIANGDONG SUN1,2,#, HUIJUAN WEN1,2,#, FAZHAN LI1,2, IHTISHAM BUKHARI1,2, FEIFEI REN1,2, XIA XUE1,2, PENGYUAN ZHENG1,2,*, YANG MI1,2,*

    Oncology Research, Vol.32, No.2, pp. 283-296, 2024, DOI:10.32604/or.2023.044618

    Abstract Nicotinamide adenine dinucleotide (NAD+) plays an essential role in cellular metabolism, mitochondrial homeostasis, inflammation, and senescence. However, the role of NAD+-regulated genes, including coding and long non-coding genes in cancer development is poorly understood. We constructed a prediction model based on the expression level of NAD+ metabolism-related genes (NMRGs). Furthermore, we validated the expression of NMRGs in gastric cancer (GC) tissues and cell lines; additionally, β-nicotinamide mononucleotide (NMN), a precursor of NAD+, was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation, cell cycle, apoptosis, and senescence-associated secretory… More > Graphic Abstract

    NAD+ associated genes as potential biomarkers for predicting the prognosis of gastric cancer

  • Open Access

    ARTICLE

    GIPC1 promotes tumor growth and migration in gastric cancer via activating PDGFR/PI3K/AKT signaling

    TINGTING LI1, WEI ZHONG1, LIU YANG1, ZHIYU ZHAO1, LI WANG1, CONG LIU1, WANYUN LI1, HAIYAN LV2, SHENGYU WANG1, JIANGHUA YAN1, TING WU1,*, GANG SONG1,*, FANGHONG LUO1,*

    Oncology Research, Vol.32, No.2, pp. 361-371, 2024, DOI:10.32604/or.2023.043807

    Abstract The high mortality rate associated with gastric cancer (GC) has resulted in an urgent need to identify novel therapeutic targets for GC. This study aimed to investigate whether GAIP interacting protein, C terminus 1 (GIPC1) represents a therapeutic target and its regulating mechanism in GC. GIPC1 expression was elevated in GC tissues, liver metastasis tissues, and lymph node metastases. GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT signaling pathway, and inhibited the proliferation and migration of GC cells. Conversely, GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway, and promoted GC cell proliferation and migration. Furthermore,… More > Graphic Abstract

    GIPC1 promotes tumor growth and migration in gastric cancer via activating PDGFR/PI3K/AKT signaling

  • Open Access

    ARTICLE

    High-throughput computational screening and in vitro evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl) phenyl]-1H-isoindole-1,3(2H)-dione (C3), as a novel EGFR—HER2 dual inhibitor in gastric tumors

    MESFER AL SHAHRANI, REEM GAHTANI, MOHAMMAD ABOHASSAN, MOHAMMAD ALSHAHRANI, YASSER ALRAEY, AYED DERA, MOHAMMAD RAJEH ASIRI, PRASANNA RAJAGOPALAN*

    Oncology Research, Vol.32, No.2, pp. 251-259, 2024, DOI:10.32604/or.2023.043139

    Abstract Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation, adhesion, angiogenesis, and metastasis. Conventional therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic mutations. Hence, dual inhibition strategies are recommended to increase potency and reduce cytotoxicity. In this study, we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase activities. Diversity-based High-throughput Virtual Screening (D-HTVS) was used to screen the whole ChemBridge small molecular library against EGFR and… More > Graphic Abstract

    High-throughput computational screening and <i>in vitro</i> evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl) phenyl]-1H-isoindole-1,3(2H)-dione (C3), as a novel EGFR—HER2 dual inhibitor in gastric tumors

  • Open Access

    ARTICLE

    Long non-coding RNA-ATB induces trastuzumab resistance and aggravates the progression of gastric cancer by repressing miR- 200c via ZNF217 elevation

    JIAZHUANG LI*, WEI ZHANG, SHOUBAO GAO, LI SUN, QINGYANG TAI, YING LIU

    BIOCELL, Vol.47, No.10, pp. 2313-2320, 2023, DOI:10.32604/biocell.2023.029860

    Abstract Background: Trastuzumab resistance accounts for chemotherapy failure in gastric cancer patients in clinical practice. The significance of long non-coding RNAs (lncRNAs) in the maintenance of drug resistance in gastric cancer has been already underlined. Method: This study aimed to identify the specific role of lncRNA-ATB in gastric cancer progression and trastuzumab resistance. The downstream miRs of lncRNA-ATB and target genes of miRs were predicted by bioinformatics analysis and verified using dual luciferase reporter assay. Loss- and gain-function assays were performed to explore the roles of lncRNA-ATB, miR-200c, and zinc-finger protein 217 (ZNF217) in the cell functions and trastuzumab resistance of… More >

  • Open Access

    ARTICLE

    Designing a risk prognosis model based on natural killer cell-linked genes to accurately evaluate the prognosis of gastric cancer

    GAOZHONG LI, FUXIN LI, NING WEI, QING JIA*

    BIOCELL, Vol.47, No.9, pp. 2081-2099, 2023, DOI:10.32604/biocell.2023.029986

    Abstract Background: This study was aimed at identifying natural killer (NK) cell-related genes to design a risk prognosis model for the accurate evaluation of gastric cancer (GC) prognosis. Methods: We obtained NK cell-related genes from various databases, followed by Cox regression analysis and molecular typing to identify prognostic genes. Various immune algorithms and enrichment analyses were used to investigate the mutations, immune status, and pathway variations among different genotypes. The key prognostic genes were assessed using the least absolute shrinkage and selection operator (Lasso) regression analysis and univariate Cox regression analysis. Thereafter, the risk score (RS) prognosis model was constructed based… More > Graphic Abstract

    Designing a risk prognosis model based on natural killer cell-linked genes to accurately evaluate the prognosis of gastric cancer

  • Open Access

    ARTICLE

    YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells

    JUNYU HE1,2,3, FENG ZENG1,2,3, XI JIN1,2,3, LIN LIANG1,2,3, MENGXIANG GAO1,2,3, WENTAO LI1,2,3, GUIYUAN LI1,2,3, YANHONG ZHOU1,2,3,*

    Oncology Research, Vol.31, No.4, pp. 615-630, 2023, DOI:10.32604/or.2023.029698

    Abstract Fos-related antigen 1 (Fra-1) is a nuclear transcription factor that regulates cell growth, differentiation, and apoptosis. It is involved in the proliferation, invasion, apoptosis and epithelial mesenchymal transformation of malignant tumor cells. Fra-1 is highly expressed in gastric cancer (GC), affects the cycle distribution and apoptosis of GC cells, and participates in GC occurrence and development. However, the detailed mechanism of Fra-1 in GC is unclear, such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis. In this study, we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) as a Fra-1-interacting protein in GC cells using co-immunoprecipitation… More >

  • Open Access

    ARTICLE

    The SMAD2/miR-4256/HDAC5/p16INK4a signaling axis contributes to gastric cancer progression

    MIN WANG1,#, HAILIANG ZHAO1,2,#, WEIWEI CHEN3,#, CAIQUN BIE4,#, JINYING YANG1, WENRUI CAI1, CHUTIAN WU1, YANFANG CHEN1, SHUFEN FENG1, YING SHI1, YUTING LI1, HUIJUN TANG4, LIXIAN ZHONG1, LILIANGZI GUO1, SISI CHEN1, LINJING LONG5, SHAOHUI TANG1,*

    Oncology Research, Vol.31, No.4, pp. 515-541, 2023, DOI:10.32604/or.2023.029101

    Abstract The dysregulation of exosomal microRNAs (miRNAs) plays a crucial role in the development and progression of cancer. This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer (GC) and the underlying mechanisms. The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics. Next, the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues, and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments. Then, the effect of miR-4256 on its downstream target genes… More > Graphic Abstract

    The SMAD2/miR-4256/HDAC5/p16<sup>INK4a</sup> signaling axis contributes to gastric cancer progression

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