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  • Open Access

    ARTICLE

    MiR-194-5p suppresses the warburg effect in ovarian cancer cells through the IGF1R/PI3K/AKT axis

    LIJUN DU1, KAIKAI DOU1, NIANHAI LIANG1,2, JIANMIN SUN1, RU BAI1,*

    BIOCELL, Vol.47, No.3, pp. 547-554, 2023, DOI:10.32604/biocell.2023.025048

    Abstract Background: The Warburg effect is considered as a hallmark of various types of cancers, while the regulatory mechanism is poorly understood. Our previous study demonstrated that miR-194-5p directly targets and regulates insulin-like growth factor1 receptor (IGF1R). In this study, we aimed to investigate the role of miR-194-5p in the regulation of the Warburg effect in ovarian cancer cells. Methods: The stable ovarian cell lines with miR-194-5p overexpression or silencing IGF1R expression were established by lentivirus infection. ATP generation, glucose uptake, lactate production and extracellular acidification rate (ECAR) assay were used to analyze the effects of aerobic glycolysis in ovarian cancer… More >

  • Open Access

    ARTICLE

    Macrophage-derived exosomal miR-342-3p promotes the progression of renal cell carcinoma through the NEDD4L/CEP55 axis

    JIAFU FENG1,2,#,*, BEI XU1,2,#, CHUNMEI DAI1,2,#, YAODONG WANG1,4, GANG XIE1,5, WENYU YANG1,2, BIN ZHANG1,2, XIAOHAN LI6, JUN WANG3

    Oncology Research, Vol.29, No.5, pp. 331-349, 2021, DOI:10.32604/or.2022.03554

    Abstract Due to its difficulty in early diagnosis and lack of sensitivity to chemotherapy and radiotherapy, renal cell carcinoma (RCC) remains to be a frequent cause of cancer-related death. Here, we probed into new targets for its early diagnosis and treatment for RCC. microRNA (miRNA) data of M2-EVs and RCC were searched on the Gene Expression Omnibus database, followed by the prediction of the potential downstream target. Expression of target genes was measured via RT-qPCR and Western blot, respectively. M2 macrophage was obtained via flow cytometry with M2-EVs extracted. The binding ability of miR-342-3p to NEDD4L and to CEP55 ubiquitination was… More >

  • Open Access

    ARTICLE

    Computational high-throughput screening and in vitro approaches identify CB-006-3; A novel PI3K-BRAFV600E dual targeted inhibitor against melanoma

    FAISAL HASSAN TOBEIGEI1, REEM M. GAHTANI2, AHMAD SHAIKH2, AMER AL ALI3, NADER KAMELI4,5, HOSSAM KAMLI2, PRASANNA RAJAGOPALAN2,6,*

    Oncology Research, Vol.29, No.5, pp. 305-318, 2021, DOI:10.32604/or.2022.025187

    Abstract Malignant melanoma is characterized by both genetic and molecular alterations that activate phosphoinositide 3-kinase (PI3K), and RAS/BRAF pathways. In this work, through diversity-based high-throughput virtual screening we identified a lead molecule that selectively targets PI3K and BRAFV600E kinases. Computational screening, Molecular dynamics simulation and MMPBSA calculations were performed. PI3K and BRAFV600E kinase inhibition was done. A375 and G-361 cells were used for in vitro cellular analysis to determine antiproliferative effects, annexin V binding, nuclear fragmentation and cell cycle analysis. Computational screening of small molecules indicates compound CB-006-3 selectively targets PI3KCG (gamma subunit), PI3KCD (delta subunit) and BRAFV600E. Molecular dynamics simulation… More >

  • Open Access

    ARTICLE

    MiR-21/Sonic Hedgehog (SHH)/PI3K/AKT Pathway is Associated with NSCLC of Primary EGFR-TKI Resistance

    Li Xu, Kang Li, Jia Li, Liyu Liu, Fang Xu, Yan Xu, Yi Kong, Xingxiang Pu, Qianzhi Wang, Jingyi Wang, Bolin Chen*, Lin Wu*

    Oncologie, Vol.24, No.3, pp. 579-590, 2022, DOI:10.32604/oncologie.2022.022121

    Abstract Background: Non-small cell lung cancer (NSCLC), caused by abnormal gene drive, may have primary drug resistance after treatment with tyrosine kinase inhibitors (EGFR-TKIs). Therefore, we explore whether the primary drug-resistant NSCLC treated with EGFR-TKI is related to the miR-21/Sonic Hedgehog (SHH)/PI3K/AKT pathway. Methods: The patients from our hospital who meet the AJCC TNM staging (7th edition) stage IIIB and stage IV NSCLC were selected in this case study. Thereafter, the treatment response of EGFR-TKIs was evaluated according to the solid tumor efficacy evaluation standard (version 1.1). The patients were divided into the EGFR-TKIs primary drug resistance group (EGFR-TKIs-Primary-R) and the… More >

  • Open Access

    REVIEW

    PI3K/AKT signaling pathway as a critical regulator of Cisplatin response in tumor cells

    ZAHRA NASRPOUR NAVAEI1, GHAZALEH KHALILI-TANHA1, AMIR SADRA ZANGOUEI2, MOHAMMAD REZA ABBASZADEGAN3, MEYSAM MOGHBELI1,3,*

    Oncology Research, Vol.29, No.4, pp. 235-250, 2021, DOI:10.32604/or.2022.025323

    Abstract Chemotherapy is one of the main therapeutic modalities for cancer patients. Cisplatin (CDDP), as one of the first-line drugs, is of great importance in the chemotherapy of various tumors. However, a significant percentage of cancer patients are resistant to CDDP treatment. Due to the CDDP side effects on normal tissues, the diagnosis of CDDP resistance is required to suggest the most efficient therapeutic strategies for cancer patients. Several molecular mechanisms and signaling pathways are associated with CDDP response. The PI3K/AKT signaling pathway has a pivotal role in the transmission of extracellular signals into the cells to regulate various pathophysiological processes… More >

  • Open Access

    ARTICLE

    Liquiritigenin Inhibits Colorectal Cancer Proliferation, Invasion, and Epithelial-to-Mesenchymal Transition by Decreasing Expression of Runt-Related Transcription Factor 2

    Fan-Chun Meng, Jun-Kai Lin

    Oncology Research, Vol.27, No.2, pp. 139-146, 2019, DOI:10.3727/096504018X15185747911701

    Abstract Inhibition of tumor metastasis is one of the most important purposes in colorectal cancer (CRC) treatment. This study aimed to explore the effects of liquiritigenin, a flavonoid extracted from the roots of Glycyrrhiza uralensis Fisch, on HCT116 cell proliferation, invasion, and epithelial-to-mesenchymal transition (EMT). We found that liquiritigenin significantly inhibited HCT116 cell proliferation, invasion, and the EMT process, but had no influence on cell apoptosis. Moreover, liquiritigenin remarkably reduced the expression of runt-related transcription factor 2 (Runx2) in HCT116 cells. Overexpression of Runx2 obviously reversed the liquiritigenininduced invasion and EMT inhibition. Furthermore, liquiritigenin inactivated the phosphoinositide 3-kinase/ protein kinase B… More >

  • Open Access

    ARTICLE

    Profilin 2 Promotes Proliferation and Metastasis of Head and Neck Cancer Cells by Regulating PI3K/AKT/b-Catenin Signaling Pathway

    Kecheng Zhou*†1, Jie Chen*†1, Jiayu Wu*†1, Yangxinzi Xu, Qiaoyun Wu*†, Jingjing Yue*†, Yu Song§, Shengcun Li*†, Peng Zhou, Wenzhan Tu*†, Guanhu Yang*†, Songhe Jiang*†

    Oncology Research, Vol.27, No.9, pp. 1079-1088, 2019, DOI:10.3727/096504019X15579146061957

    Abstract Profilin 2 (PFN2) was found to be mainly expressed in neurons and involved in the development of the brain. In recent years, emerging evidence indicated that PFN2 is also significantly upregulated in various cancers including head and neck cancer (HNSC) and influences cancer cell proliferation, migration, and invasion. However, the role of PFN2 in HNSC development and progression remains unclear. The aim of our study was to investigate the role of PFN2 in the development of HNSC and its possible molecular mechanisms. Bioinformatics showed that increased expression of PFN2 in tumors correlated highly with poor prognosis of HNSC patients. Our… More >

  • Open Access

    ARTICLE

    CRISPR/Cas9-Mediated Gene Knockout of ARID1A Promotes Primary Progesterone Resistance by Downregulating Progesterone Receptor B in Endometrial Cancer Cells

    Haizhen Wang*, Zhenghua Tang*, Ting Li*, Menglu Liu*, Yong Li, Baoling Xing*

    Oncology Research, Vol.27, No.9, pp. 1051-1060, 2019, DOI:10.3727/096504019X15561873320465

    Abstract Medroxyprogesterone (MPA) is used for the conservative treatment of endometrial cancer. Unfortunately, progesterone resistance seriously affects its therapeutic effect. The purpose of the current study was to investigate the influence of deletion of AT-rich interactive domain 1A (ARID1A) in progesterone resistance in Ishikawa cells. Ablation of ARID1A was conducted through the CRISPR/Cas9 technology. Acquired progesterone-resistant Ishikawa (Ishikawa-PR) cells were generated by chronic exposure of Ishikawa cells to MPA. The sensitivity of the parental Ishikawa, Ishikawa-PR, and ARID1A-deficient cells to MPA and/or LY294002 was determined using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. In addition, Western blot analysis… More >

  • Open Access

    ARTICLE

    PD-L1 Induces Epithelial–Mesenchymal Transition in Nasopharyngeal Carcinoma Cells Through Activation of the PI3K/AKT Pathway

    Zhenghua Fei*1, Zhenxiang Deng†1, Lingyang Zhou, Kejie Li*, Xiaofang Xia*, Raoying Xie*

    Oncology Research, Vol.27, No.7, pp. 801-807, 2019, DOI:10.3727/096504018X15446984186056

    Abstract Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma of the head and neck. Cancer therapy targeting programmed cell death protein-1 (PD-1) or programmed death ligand-1 (PD-L1) is revolutionary. However, the tumorigenic mechanism of PD-L1 is not yet clear in NPC. Here we demonstrated an oncogenic role of PD-L1 via activating PI3K/AKT in NPC cells. PD-L1 overexpression was frequently detected in NPC biopsies and cell lines by qRT-PCR. PD-L1 overexpression and knockdown demonstrated that PD-L1 promoted NPC cell invasion and metastasis in vitro and in vivo. Mechanistically, PD-L1 prominently activated the epithelial–mesenchymal transition (EMT) process in a PI3K/AKT-dependent manner. Taken together,… More >

  • Open Access

    ARTICLE

    Silencing of NADPH Oxidase 4 Attenuates Hypoxia Resistance in Neuroblastoma Cells SH-SY5Y by Inhibiting PI3K/Akt-Dependent Glycolysis

    Ting Yu*1, Lei Li†1, Wenyan Liu*, Bailiu Ya*, Hongju Cheng*, Qing Xin*

    Oncology Research, Vol.27, No.5, pp. 525-532, 2019, DOI:10.3727/096504018X15179668157803

    Abstract Hypoxia-induced chemoresistance is a major obstacle in the development of effective cancer therapy. In our study, the reversal abilities of NADPH oxidase 4 (NOX4) silence on hypoxia resistance and the potential mechanism were investigated. Our data showed that the expression of NOX4 was upregulated in human neuroblastoma cells SH-SY5Y under hypoxia condition time dependently. Knockdown of NOX4 expression by siRNA inhibited glycolysis induced by hypoxia through decreasing the expression of glycolysis-related proteins (HIF-1 , LDHA, and PDK1), decreasing glucose uptake, lactate production, and ROS production, while increasing mitochondria membrane potential. Moreover, NOX4 silence inhibited cell growth under hypoxia condition through… More >

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