scholarly journals Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21

2021 ◽  
Vol 9 ◽  
Author(s):  
Peng Chen ◽  
Zhiwei He ◽  
Jie Wang ◽  
Jian Xu ◽  
Xueyi Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Cycle Progression ◽  
Bioinformatic Analysis ◽  
Vital Role ◽  
Luciferase Assay ◽  
Tissue Array ◽  
Cancer Proliferation ◽  
Mrna And Protein Expression ◽  
P53 Activation

p53/p21 signaling plays a vital role in pancreatic cancer (PC) progression. ZWINT was shown to function as an oncoprotein in the progression of multiple cancers. However, the involvement of ZWINT and p53 activation in the progression of PC remains poorly understood. Bioinformatics and tissue array chip analyses were performed to evaluate ZWINT expression in pancreatic cancer. ZWINT mRNA and protein expression were evaluated in normoxia and hypoxia. CHIP was used to evaluate HIF1α interaction with the ZWINT promoter. CCK8, colony formation, EDU, and cell cycle analysis were used to examine PC cell proliferation. Immunoprecipitation and immunofluorescence were used to examine the interaction of ZWINT, MDM2, and p53. p53 activity was evaluated by q-PCR and luciferase assay. Protein degradation and ubiquitination assays were used to analyze the role of ZWINT in p53 ubiquitination. ZWINT was overexpressed in pancreatic cancer and induced in hypoxia. ZWINT promoted pancreatic cancer growth and cell cycle progression. Bioinformatic analysis revealed that ZWINT may regulate the p53 signal pathway. ZWINT interacts with p53 and promotes its ubiquitination and degradation. ZWINT promoted proliferation via p53/p21. Immunohistochemistry of clinical specimens revealed that that ZWINT expression was significantly negatively correlated with p53/p21. Our data showed that hypoxia regulates the expression of ZWINT, which activated p53/p21 signaling pathway to promote PC growth.

scholarly journals Over-expression of ANP32E is associated with poor prognosis of pancreatic cancer and promotes cell proliferation and migration through regulating β-catenin

2020 ◽  
Author(s):  
Jianwei Zhang ◽  
Zhongmin Lan ◽  
Guotong Qiu ◽  
Hu Ren ◽  
Yajie Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Cell Cycle Progression ◽  
Over Expression ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Abstract Background: Pancreatic cancer is a malignant tumor with high mortality. Acidic nuclear phosphoprotein 32 family member E (ANP32E), a specific H2A.Z chaperone, has been shown to contribute to breast cancer development. However, the significance of ANP32E in pancreatic cancer is poorly understood. This study aimed to investigate the role of ANP32E in pancreatic cancer. Methods: The expression of ANP32E in 179 pancreatic cancer tissues and 171 normal tissues, and the correlation between ANP32E expression and patients’ survival were analyzed from the TCGA database. ANP32E was over-expressed and silenced using lentivirus. siRNA was used to knock down β-catenin. CCK8, colony formation, cell cycle and transwell experiments were performed to determine cell proliferation and migration. qRT-PCR and Western blot were conducted to detect mRNA and protein expression. Results: ANP32E was up-regulated in pancreatic cancer tissues and cells. Up-regulation of ANP32E predicted poor prognosis in pancreatic cancer patients. Lentivirus-mediated knockdown of ANP32E suppressed the proliferation, colony growth and migration of PANC1 and MIA cells. By contrast, ANP32E over-expression promoted the proliferation and migration of both cells. In addition, ANP32E accelerated the cell cycle progression in PANC1 and MIA cells. Molecular experiments showed that ANP32E activated β-catenin/cyclin D1 signaling. Silencing of β-catenin reduced cell proliferation and migration in ANP32E over-expressed cells. Conclusion: Our results propose that ANP32E functions as an oncogene in pancreatic cancer via activating β-catenin.

scholarly journals GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway

2020 ◽  
Vol 11 (16) ◽  
pp. 4662-4670
Author(s):  
Miao Zhang ◽  
Saifei He ◽  
Xing Ma ◽  
Ying Ye ◽  
Guoyu Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Cell Cycle Progression ◽  
Erk Pathway ◽  
Cycle Progression ◽  
Pancreatic Cancer Cells

scholarly journals Over-expression of ANP32E is associated with poor prognosis of pancreatic cancer and promotes cell proliferation and migration through regulating β-catenin

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jianwei Zhang ◽  
Zhongmin Lan ◽  
Guotong Qiu ◽  
Hu Ren ◽  
Yajie Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Cell Cycle Progression ◽  
Over Expression ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Abstract Background Pancreatic cancer is a malignant tumor with high mortality. Acidic nuclear phosphoprotein 32 family member E (ANP32E), a specific H2A.Z chaperone, has been shown to contribute to breast cancer development. However, the significance of ANP32E in pancreatic cancer is poorly understood. This study aimed to investigate the role of ANP32E in pancreatic cancer. Methods The expression of ANP32E in 179 pancreatic cancer tissues and 171 normal tissues, and the correlation between ANP32E expression and patients’ survival were analyzed from the TCGA database. ANP32E was over-expressed and silenced using lentivirus. siRNA was used to knock down β-catenin. CCK8, colony formation, cell cycle and transwell experiments were performed to determine cell proliferation and migration. qRT-PCR and Western blot were conducted to detect mRNA and protein expression. Results ANP32E was up-regulated in pancreatic cancer tissues and cells. Up-regulation of ANP32E predicted poor prognosis in pancreatic cancer patients. Lentivirus-mediated knockdown of ANP32E suppressed the proliferation, colony growth and migration of PANC1 and MIA cells. By contrast, ANP32E over-expression promoted the proliferation and migration of both cells. In addition, ANP32E accelerated the cell cycle progression in PANC1 and MIA cells. Molecular experiments showed that ANP32E activated β-catenin/cyclin D1 signaling. Silencing of β-catenin reduced cell proliferation and migration in ANP32E over-expressed cells. Conclusion Our results propose that ANP32E functions as an oncogene in pancreatic cancer via activating β-catenin.

scholarly journals Cdc6 disruption leads to centrosome abnormalities and chromosome instability in pancreatic cancer cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuna Youn ◽  
Jong-chan Lee ◽  
Jaihwan Kim ◽  
Jae Hyeong Kim ◽  
Jin-Hyeok Hwang
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Chromosome Instability ◽  
The Cancer Genome Atlas ◽  
M Cell ◽  
Pancreatic Cancer Cells ◽  
Potential Biomarker ◽  
Cancer Genome Atlas

Abstract Cell division cycle 6 (Cdc6) plays key roles in regulating DNA replication, and activation and maintenance of cell cycle check points. In addition, Cdc6 exerts oncogenic properties via genomic instability associated with incomplete DNA replication. This study aimed to examine the effects of Cdc6 on pancreatic cancer (PC) cells. Our results showed that Cdc6 expression was higher in clinical PC specimens (based on analysis of the GEPIA database) and cell lines, and the high Cdc6 expression was associated with poorer survival in The Cancer Genome Atlas-PC cohort. In addition, Cdc6-depleted PC cells significantly inhibited cell proliferation and colony formation, delayed G2/M cell cycle progression, and increased expression of p-histone H3 and cyclin A2 levels. These observations could be explained by Cdc6 depletion leading to multipolar and split spindles via centrosome amplification and microtubule disorganization which eventually increases chromosome missegregation. Furthermore, Cdc6-depleted PC cells showed significantly increased apoptosis, which was consistent with increased caspase-9 and caspase-3 activation. Collectively, our results demonstrated that Cdc6-depleted PC cells are arrested in mitosis and eventually undergo cell death by induced multipolar spindles, centrosome aberrations, microtubule disorganization, and chromosome instability. In conclusion, Cdc6 may be a potential biomarker and therapeutic target for PC.

scholarly journals Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases

Cancer Cell ◽  
2019 ◽  
Vol 35 (2) ◽  
pp. 267-282.e7 ◽  
Author(s):  
Ashton A. Connor ◽  
Robert E. Denroche ◽  
Gun Ho Jang ◽  
Mathieu Lemire ◽  
Amy Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Cycle Progression ◽  
Cycle Progression

scholarly journals MiR-15b Targets Cyclin D1 to Regulate Proliferation and Apoptosis in Glioma Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Guan Sun ◽  
Lei Shi ◽  
Shushan Yan ◽  
Zhengqiang Wan ◽  
Nan Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Therapeutic Strategy ◽  
Glioma Cells ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Proliferation And Apoptosis

Aim. To investigate the role and mechanism of miR-15b in the proliferation and apoptosis of glioma.Methods. The miR-15b mimics were transfected into human glioma cells to upregulate the miR-15b expression. Cyclin D1 was determined by both western blotting analysis and luciferase reporter assay. Methylthiazol tetrazolium (MTT) and flow cytometry were employed to detect the cell proliferation, cell cycle, and apoptosis.Results. Overexpression of miR-15b inhibits proliferation by arrested cell cycle progression and induces apoptosis, possibly by directly targeting Cyclin D1. Both luciferase assay and bioinformatics search revealed a putative target site of miR-15b binding to the 3′-UTR of Cyclin D1. Moreover, expression of miR-15b in glioma tissues was found to be inversely correlated with Cyclin D1 expression. Enforced Cyclin D1 could abrogate the miR-15b-mediated cell cycle arrest and apoptosis.Conclusions. Our findings identified that miR-15b may function as a glioma suppressor by targeting the Cyclin D1, which may provide a novel therapeutic strategy for treatment of glioma.

scholarly journals MicroRNA-378a-3p is overexpressed in psoriasis and modulates cell cycle arrest in keratinocytes via targeting BMP2 gene

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wipasiri Soonthornchai ◽  
Pattarin Tangtanatakul ◽  
Kornvalee Meesilpavikkai ◽  
Virgil Dalm ◽  
Patipark Kueanjinda ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Gene Expression Regulation ◽  
Mechanistic Model ◽  
Ultraviolet B ◽  
Bone Morphogenetic Protein 2 ◽  
Luciferase Assay ◽  
Cycle Arrest

AbstractPsoriasis is a chronic autoimmune skin disease driven by dysregulations at the cellular, genomic and genetic levels. MicroRNAs are key mediators of gene expression regulation. However, how microRNAs control the pathogenesis of psoriasis is still unclear. Here, we reported a significant up-regulation of miR-378a-3p (miR-378a) in skin biopsies from active psoriatic lesions while it was down-regulated after treatment with methotrexate or narrow-band ultraviolet B phototherapy. Using the keratinocyte in vitro model, we showed that miR-378a disturbed the cell cycle progression, causing cell cycle arrest at G1 phase. Transcriptomic analysis of keratinocytes with miR-378a overexpression and depletion revealed several important biological mechanisms related to inflammation and tight junction. Target mRNA transcript assessed by luciferase assay identified bone morphogenetic protein 2 as a novel target gene of miR-378a. These findings offer a mechanistic model where miR-378a contributes to the pathogenesis of psoriasis.

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