scholarly journals EBV-BZLF1 Promotes Gastric Cancer Growth Through Activating the PI3K/AKT Pathway

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 218s-218s
Author(s):  
B. Li ◽  
M. Zhang ◽  
C. Zhang ◽  
L. Shen ◽  
J. Gao
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Treatment Options ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
P53 Expression ◽  
P53 Signaling ◽  
Phase Arrest ◽  
Lentiviral Infection

Background: EBVaGC (EBV associated gastric cancer) had been paid much attentions once classified by TCGA and were considered as the suitable group for immunotherapy, which hold distinguishing characteristics with EBVnGC (EBV nonassociated gastric cancer). This study aims to explore the biologic behavior and its possible mechanisms to provide treatment options for EBVaGC. Methods: Lentiviral infection system was used to construct the control and BZLF1 stably expressing gastric cancer cell lines (AGS and HGC27). The cell-derived xenografts (CDX) were constructed to detect the tumor growth and functional experiment including CCK8 assay, cell cycle assay, apoptosis assay, cell migration and invasion assay were implemented to detect the proliferation and transfer ability in vitro. Western blot and immunohistochemistry were used to detect the expression of related molecules. Results: The BZLF1 overexpression cells and the corresponding xenografts grew faster than control groups with enhanced pAKT and pS6 expression. BZLF1 induced “G0/1 phase” arrest in AGS and “S phase” arrest in HGC27 cell, inhibited cell apoptosis through upregulating bcl-2 protein, meanwhile, slightly increased P53 and p-P53 expression in both BZLF1 overexpression cells. However, no significant effects were observed on the malignant biologic behaviors in terms of migration and invasion ability. Conclusion: BZLF1 may promote the growth of gastric cancer through activating the PI3K/AKT pathway, regulating the cell cycle especially regarding P53 signaling network. PI3K/AKT pathway inhibitor probably become promising treatment options for EBVaGC.

PGM1 Suppresses Colorectal Cancer Cell Migration And Invasion by Regulating PI3K/ AKT Pathway

2021 ◽  
Author(s):  
Zhewen Zheng ◽  
Xue Zhang ◽  
Jian Bai ◽  
Long Long ◽  
Di Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colony Formation ◽  
Tumor Formation ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Cycle Arrest ◽  
Cancer Pathogenesis

Abstract BackgroundPhosphoglucomutase 1(PGM1) is known for its involvement in cancer pathogenesis. However, its biological role in colorectal cancer (CRC) is unknown. Here, we studied the functions and mechanisms of PGM1 in CRC.Methods We verified PGM-1 as a DEG by a comprehensive strategy of the TCGA-COAD dataset mining and computational biology. Relative levels of PGM-1 in CRC tumors and adjoining peritumoral tissue were identified by qRT-PCR, WB, and IHC staining in a tissue microarray. PGM1 functions were analyzed using CCK8, EdU, colony formation, cell cycle, apoptosis, and Transwell migration and invasion assays. The influence of PGM1 was further investigated using tumor formation in vivo.ResultsPGM1 mRNA and protein were both reduced in CRC and the reduction was related to CRC pathology and overall survival. PGM1 knockdown stimulated both proliferation and colony formation, promoting cell cycle arrest and apoptosis while overexpression has opposite effects in CRC cells both in vivo and in vitro. Furthermore, we lined the actions of PGM1 to the PI3K/ AKT pathway. ConclusionWe verified that PGM1 suppresses CRC through the PI3K/ AKT pathway. These results suggest the potential for targeting PGM1 in CRC therapies.

scholarly journals Upregulated TRIM11 Exerts its Oncogenic Effects in Hepatocellular Carcinoma Through Inhibition of P53

2017 ◽  
Vol 44 (1) ◽  
pp. 255-266 ◽  
Author(s):  
Jinjin Liu ◽  
Jun Rao ◽  
Xuming Lou ◽  
Jian Zhai ◽  
Zhenhua Ni ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Development ◽  
Tumor Model ◽  
Migration And Invasion ◽  
P53 Expression ◽  
Protein Levels ◽  
Normal Tissues ◽  
P53 Signaling

Background/Aims: The tripartite motif containing (TRIM) family plays crucial roles in tumor development and progression. However, little is known about the function and mechanism of TRIM11 in hepatocellular carcinoma (HCC). Methods: The expression levels of TRIM11 were examined by real-time PCR, Western blot and Immunohistochemical (IHC) staining. TRIM11 knockdown cells were produced by lentivirus infection, and functional assays, such as MTT, colony formation assay, migration and invasion assays and a xenograft tumor model were used to investigate the role of TRIM11 in HCC. We also determined the effect of TRIM11 on p53 signaling and its downstream molecules. Results: We found that TRIM11 mRNA and protein levels were significantly increased in HCC tissues as compared with normal tissues; increased levels correlated with poor patient survival. By loss- and gain-of-function investigations, knockdown of TRIM11 suppressed cell proliferation, migration, invasion in vitro and tumor growth in vivo. Moreover, TRIM11 negatively regulated p53 expression. Knockdown of p53 abrogated the in vitro and in vivo biological functions of TRIM11 shRNA in HCC cells. Conclusions: These data show that TRIM11 exerts its oncogenic effect in HCC by downregulating p53 both in vitro and in vivo. Our data provide new insights into the pathogenesis of HCC and indicate that TRIM11 may serve as a new therapeutic target for HCC treatment.

scholarly journals hsa_circ_0023409 Accelerates Gastric Cancer Cell Growth and Metastasis Through Regulating the IRS4/PI3K/AKT Pathway

2021 ◽  
Vol 30 ◽  
pp. 096368972097539
Author(s):  
Jian Li ◽  
Yongjing Yang ◽  
Dequan Xu ◽  
Ling Cao
Keyword(s):  
Gastric Cancer ◽  
Histological Grade ◽  
Human Life ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Circular Rnas

Gastric cancer (GC) is a big threat to human life and health. Circular RNAs (circRNAs), a subclass of noncoding RNAs, were reported to play a critical role in GC progression. Here, we investigated the role of a novel circRNA named hsa_circ_0023409 in GC and its mechanism. Hsa_circ_0023409 expression in GC and adjacent tissues was examined by quantitative real-time polymerase chain reaction and in situ hybridization. The functions of hsa_circ_0023409 in GC cells were assessed both in vitro and in vivo. Immunofluorescence staining was performed for the localization of hsa_circ_0023409 and miR-542-3p in cells. The interaction between hsa_circ_0023409 and miR-542-3p, and miR-542-3p and insulin receptor substrate 4 (IRS4) was detected by dual-luciferase reporter assay. The effect of hsa_circ_0023409, miR-542-3p, and IRS4 on IRS4/phosphatidylinositol 3-kinase (PI3K)/AKT pathway was detected by western blot. The results showed that hsa_circ_0023409 was mainly located in cytoplasm and highly expressed in GC tissues and cells. Moreover, hsa_circ_0023409 showed positive correlation with tumor size, histological grade, and tumor–node–metastasis staging of GC patients. Functional studies showed that hsa_circ_0023409 promoted cell viability, proliferation, migration, and invasion and suppressed apoptosis in GC. Mechanism studies demonstrated that hsa_circ_0023409 upregulated IRS4 via sponging miR-542-3p in GC cells. Furthermore, IRS4 overexpression activated the PI3K/AKT pathway and reversed the inhibitory effect of hsa_circ_0023409 knockdown on the PI3K/AKT pathway. Taken together, we prove that hsa_circ_0023409 activates IRS4/PI3K/AKT pathway by acting as a sponge for miR-542-3p, thus promoting GC progression, indicating that hsa_circ_0023409 may serve as a potential target for treatment of GC and prognosis of GC patients.

Knockdown of KREMEN2 inhibits tumor proliferation and metastasis in gastric cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16555-e16555
Author(s):  
Beibei Chen ◽  
Saiqi Wang ◽  
Jinxi Huang ◽  
Jitian Li ◽  
Jianying Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Gastric Cancer Cell ◽  
Akt Pathway ◽  
Gastric Cancer Cells ◽  
The Relationship

e16555 Background: KREMEN2 is an important regulator of classical Wnt/β-catenin signaling pathway. However, the relationship between KREMEN2 and gastric cancer is not clear. The aim of this study was to explore the regulatory role of KREMEN2 in the tumorigenesis and metastasis of gastric cancer. Methods: We measured the protein level of KREMEN2 in 156 gastric adenocarcinoma, 40 metastatic gastric adenocarcinoma, 8 marginal and 4 normal tissues using tissue microarray. The differences in KREMEN2 expression were tested with Mann-Whitney U test. The relationship between KREMEN2 expression and pathologic data was determined with Pearson’s correlation analysis. The mRNA and protein level in cultured cell lines were detected by qRT-PCR and western blotting, respectively. Lentivirus was transfected by repressing KREMEN2. Cell viability was determined by the MTT assay. Apoptosis and cell cycle distribution were detected using flow cytometry. The cell migration was investigated by wound healing and transwell assay. Antibody array was performed to explore the underlying molecule mechanism. In vivo, Xenograft assay was established using nude mice to explore the role of KREMEN2 in gastric cancer cell and bioluminescence was observed via an in vivo imaging system. Results: It was demonstrated that, compared to para-cancerous tissues, KREMEN2 was significantly up-regulated in gastric cancer tissues, and was positively correlated with the pathological grade of gastric cancer patients. Given that KREMEN2 is abundantly expressed in most tested gastric cancer cell lines, KREMEN2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down KREMEN2, the proliferation of gastric cancer cells was inhibited both in vivo and in vitro. At the same time, knockdown of KREMEN2 induced apoptosis, cell cycle arrest at G2/M phase and inhibition of migration in gastric cancer cells in vitro. Mechanistically, we found that knockdown of KREMEN2 suppressed PI3K/Akt pathway. Conclusions: Therefore, we revealed that the overexpression of KREMEN2 in gastric cancer may promote the carcinogenesis and metastasis of gastric cancer by activating the PI3K/Akt pathway.

scholarly journals NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Yuanbo Hu ◽  
Chenbin Chen ◽  
Xinya Tong ◽  
Sian Chen ◽  
Xianjing Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Treatment Options ◽  
Biological Significance ◽  
Tissue Microarrays ◽  
Migration And Invasion ◽  
Multiple Cancer ◽  
Carcinogenic Activity

AbstractThe 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is involved in the regulation of cell proliferation and metastasis formation and is upregulated in multiple cancers. However, the biological significance of NSUN2 in gastric cancer (GC) and the modification of NSUN2 itself have not been fully investigated. Here, we analyzed the expression level of NSUN2 in tissue microarrays containing 403 GC tissues by immunohistochemistry. NSUN2 was upregulated in GC, and that it was a predictor of poor prognosis. NSUN2 promotes the proliferation, migration, and invasion of GC cells in vitro. We also demonstrated that small ubiquitin-like modifier (SUMO)-2/3 interacts directly with NSUN2 by stabilizing it and mediating its nuclear transport. This facilitates the carcinogenic activity of NSUN2. Furthermore, m5C bisulfite sequencing (Bis-seq) in NSUN2-deficient GC cells showed that m5C-methylated genes are involved in multiple cancer-related signaling pathways. PIK3R1 and PCYT1A may be the target genes that participate in GC progression. Our findings revealed a novel mechanism by which NSUN2 functions in GC progression. This may provide new treatment options for GC patients.

scholarly journals Pinocembrin Inhibits the Proliferation and Metastasis of Breast Cancer via Suppression of the PI3K/AKT Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinbing Zhu ◽  
Rongnian Li ◽  
Chen Wang ◽  
Shuo Zhou ◽  
Yujia Fan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Anticancer Activities ◽  
Phase Arrest ◽  
Low Concentrations ◽  
M Phase

The survival rate of breast cancer (BC) patients remains poor, thus the identification of safe and effective new drugs is crucial to improve therapeutic outcomes and overall survival. Pinocembrin (PCB), a pharmacologically active ingredient of Pinus heartwood, Eucalyptus, Euphorbia, Populus, and Sparattosperma leucanthum, has been widely applied for the treatment of various diseases and possesses anticancer activities. In vitro assays were performed to investigate the antiproliferation and antimetastasis activities of PCB in BC cells. A tumorigenesis assay with the use of murine BC models was performed to assess the antiproliferation activities of PCB in vivo. Moreover, the molecular mechanisms underlying the anticancer activities of PCB in BC cells were explored. The results showed that the anti-inhibitory and antiproliferation activities of PCB in BC might involve cell cycle (G2/M phase) arrest and apoptosis. PCB downregulated the expression levels of proteins involved in cell cycle progression and apoptosis, including cyclinB1, Cdc2, PARP1, Bcl-2, and survivin, and upregulated protein levels of cleaved PARP1, cleaved caspase3, cleaved caspase9, and BAX. In a murine subcutaneous tumor model, PCB suppressed the growth of MCF-7 cells in vivo. Low concentrations of PCB also significantly inhibited the migration and invasion abilities of BC cells. Mechanistically, PCB administration was correlated to suppression of the PI3K/AKT signaling pathway. Inhibition of the proliferation of BC cells by PCB involved cell cycle (G2/M phase) arrest and apoptosis in vitro and in vivo. Low concentrations of PCB also significantly inhibited the migration and invasion abilities of BC cells. These findings suggest that PCB might be an effective agent for treatment of BC patients.

OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction

2020 ◽  
Vol 20 ◽  
Author(s):  
En Xu ◽  
Hao Zhu ◽  
Feng Wang ◽  
Ji Miao ◽  
Shangce Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Cell Counting ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Dual Inhibitor ◽  
Induced Apoptosis

: Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.

Cyclosporine A Suppresses the Malignant Progression of Oral Squamous Cell Carcinoma in vitro

2019 ◽  
Vol 19 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Ling Gao ◽  
Jianwei Dong ◽  
Nanyang Zhang ◽  
Zhanxian Le ◽  
Wenhao Ren ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cyclosporine A ◽  
Migration And Invasion ◽  
Signal Molecules ◽  
Cox 2

Background:The Oral Squamous Cell Carcinoma (OSCC) is one of the most frequent cancer types. Failure of treatment of OSCC is potentially lethal because of local recurrence, regional lymph node metastasis, and distant metastasis. Chemotherapy plays a vital role through suppression of tumorigenesis. Cyclosporine A (CsA), an immunosuppressant drug, has been efficiently used in allograft organ transplant recipients to prevent rejection, and also has been used in a subset of patients with autoimmunity related disorders. The present study aims to investigate novel and effective chemotherapeutic drugs to overcome drug-resistance in the treatment of OSCC.Methods:Cells were incubated in the standard way. Cell viability was assayed using the MTT assay. Cell proliferation was determined using colony formation assay. The cell cycle assay was performed using flow cytometry. Apoptosis was assessed using fluorescence-activated cell sorting after stained by the Annexin V-fluorescein isothiocyanate (FITC). Cell migration and invasion were analyzed using wound healing assay and tranwell. The effect of COX-2, c-Myc, MMP-9, MMP-2, and NFATc1 protein expression was determined using Western blot analysis while NFATc1 mRNA expression was determined by RT-PCR.Results:In vitro studies indicated that CsA inhibited partial OSCC growth by inducing cell cycle arrest, apoptosis, and the migration and invasion of OSCC cells. We also demonstrated that CsA could inhibit the expression of NFATc1 and its downstream genes COX-2, c-Myc, MMP-9, and MMP-2 in OSCC cells. Furthermore, we analyzed the expression of NFATc1 in head and neck cancer through the Oncomine database. The data was consistent with the experimental findings.Conclusion:The present study initially demonstrated that CsA could inhibit the progression of OSCC cells and can mediate the signal molecules of NFATc1 signaling pathway, which has strong relationship with cancer development. That explains us CsA has potential to explore the possibilities as a novel chemotherapeutic drug for the treatment of OSCC.

scholarly journals miR-29a sensitizes the response of glioma cells to temozolomide by modulating the P53/MDM2 feedback loop

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Qiudan Chen ◽  
Weifeng Wang ◽  
Shuying Chen ◽  
Xiaotong Chen ◽  
Yong Lin
Keyword(s):  
Molecular Mechanism ◽  
Feedback Loop ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Aberrant Expression ◽  
Altered Expression ◽  
P53 Signaling

AbstractRecently, pivotal functions of miRNAs in regulating common tumorigenic processes and manipulating signaling pathways in brain tumors have been recognized; notably, miR‐29a is closely associated with p53 signaling, contributing to the development of glioma. However, the molecular mechanism of the interaction between miR-29a and p53 signaling is still to be revealed. Herein, a total of 30 glioma tissues and 10 non-cancerous tissues were used to investigate the expression of miR‐29a. CCK-8 assay and Transwell assay were applied to identify the effects of miR-29a altered expression on the malignant biological behaviors of glioma cells in vitro, including proliferation, apoptosis, migration and invasion. A dual-luciferase reporter assay was used to further validate the regulatory effect of p53 or miR-29a on miR-29a or MDM2, respectively, at the transcriptional level. The results showed that miR-29a expression negatively correlated with tumor grade of human gliomas; at the same time it inhibited cell proliferation, migration, and invasion and promoted apoptosis of glioma cells in vitro. Mechanistically, miR-29a expression was induced by p53, leading to aberrant expression of MDM2 targeted by miR-29a, and finally imbalanced the activity of the p53-miR-29a-MDM2 feedback loop. Moreover, miR-29a regulating p53/MDM2 signaling sensitized the response of glioma cells to temozolomide treatment. Altogether, the study demonstrated a potential molecular mechanism in the tumorigenesis of glioma, while offering a possible target for treating human glioma in the future.

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