scholarly journals miR-192 Is Overexpressed and Promotes Cell Proliferation in Prostate Cancer

2018 ◽  
Vol 28 (2) ◽  
pp. 124-132 ◽  
Author(s):  
Zhong-Jun  Chen ◽  
You-Ji Yan ◽  
Hao Shen ◽  
Jia-Jie Zhou ◽  
Guang-Hua Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Functional Roles ◽  
Normal Tissues ◽  
Cancer Genome Atlas

Objective: Prostate cancer (PCa) is one of the most prevalent types of cancer among men worldwide. The incidence of PCa is increasing in China. Therefore, there is an urgent need to identify novel diagnostic and prognostic markers for PCa to improve the treatment of the disease. Methods: The Cancer Genome Atlas (TCGA) and GEO database were used to analyze the expression of miR-192, and the relationship between miR-192 and the clinical features of patients with PCa. Cell cycle and cell proliferation assay were used to detect the functional roles of miR-192 in PCa. Bioinformatic analysis for miR-192–5p was performed using gene ontology and KEGG analysis. Results: By analyzing the dataset of TCGA, we found that miR-192 was overexpressed in PCa samples compared to normal tissues and was upregulated in high-grade PCa compared to low-grade PCa. We also observed that higher miR-192 expression was associated with a shorter biochemical recurrence-free survival time. Our results also demonstrated that miR-192 promoted PCa cell proliferation and cell cycle progression. Conclusion: These results suggest that miR-192 may be considered for use as a potential diagnostic and therapeutic target of PCa.

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 FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hongbo Yu ◽  
Zheng Xu ◽  
Maomao Guo ◽  
Weiwan Wang ◽  
Weican Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Cell Cycle Progression ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Docetaxel Resistance ◽  
Apoptosis Protein

Abstract Background Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. Transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers. Methods We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using a ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity. Results FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found that FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion. Conclusions Our findings indicate that highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

scholarly journals FOXM1  modulates docetaxel resistance in prostate cancer by regulating KIF20A

2020 ◽  
Author(s):  
Hongbo Yu ◽  
Zheng Xu ◽  
Maomao Guo ◽  
Weiwan Wang ◽  
Weican Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Cell Cycle Progression ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Docetaxel Resistance ◽  
Apoptosis Protein

Abstract Background: Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. The transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers.Methods: We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using the ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity.Results: FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion.Conclusions: Our findings indicate highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

scholarly journals Systematic analysis of aberrances of ferroptosis reveals its potential functional roles in cancer

2019 ◽  
Author(s):  
Zekun Liu ◽  
Qi Zhao ◽  
Zhi-Xiang Zuo ◽  
Shu-Qiang Yuan ◽  
Kai Yu ◽  
...  
Keyword(s):  
The Cancer Genome Atlas ◽  
Copy Number Alterations ◽  
Aberrant Expression ◽  
Systematic Analysis ◽  
Functional Roles ◽  
Normal Tissues ◽  
Potential Index ◽  
Cancer Genome Atlas ◽  
Regulator Genes ◽  
Worse Prognosis

SummaryFerroptosis is a type of cell death that related to cancer, however, the characteristics of ferroptosis in cancers are still uncertain. Based on the data in The Cancer Genome Atlas, we found that most ferroptosis regulator genes (FRGs) were differentially expressed in tumors, copy number alterations (CNA) and DNA methylation contributed to their aberrant expression. We established the ferroptosis potential index (FPI) to reveal the functional roles of ferroptosis and noticed that the FPI was higher in tumors than in normal tissues in most cancers, and was associated with subtypes and clinical features. The FPI was negatively correlated with several metabolism pathways but positively associated with several important metastasis-related pathways and immune-related pathways. Higher FPI predicted worse prognosis in several tumors, while FPI and FRGs impacted drug sensitivity. Our study presents a systematical analysis of ferroptosis and its regulatory genes, and highlights the potential of ferroptosis-based cancer therapy.

scholarly journals BRG1 promotes transcriptional patterns that are permissive to proliferation in cancer cells

2020 ◽  
Author(s):  
Katherine A. Giles ◽  
Cathryn M. Gould ◽  
Joanna Achinger-Kawecka ◽  
Scott G. Page ◽  
Georgia Kafer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
The Cancer Genome Atlas ◽  
G1 Arrest ◽  
Cycle Progression ◽  
Prostate Cell ◽  
Wide Range ◽  
Transcriptional Changes

ABSTRACTBackgroundBRG1 (encoded by SMARCA4) is a catalytic component of the SWI/SNF chromatin remodelling complex, with key roles in modulating DNA accessibility. Dysregulation of BRG1 is observed, but functionally uncharacterised, in a wide range of malignancies. We have probed the functions of BRG1 on a background of prostate cancer to investigate how BRG1 controls gene expression programs and cancer cell behaviour.ResultsOur investigation of SMARCA4 revealed that BRG1 is universally overexpressed in 486 tumours from The Cancer Genome Atlas prostate cohort, as well as in a complementary panel of 21 prostate cell lines. Next, we utilised a temporal model of BRG1 depletion to investigate the molecular effects on global transcription programs. Unexpectedly, depleting BRG1 had no impact on alternative splicing and conferred only modest effect on global expression. However, of the transcriptional changes that occurred, most manifested as down-regulated expression. Deeper examination found the common thread linking down-regulated genes was involvement in proliferation, including several known to increase prostate cancer proliferation (KLK2, PCAT1 and VAV3). Interestingly, the promoters of genes driving proliferation were bound by BRG1 as well as the oncogenic transcription factors, AR and FOXA1. We also noted that BRG1 depletion repressed genes involved in cell cycle progression and DNA replication but intriguingly, these pathways operated independently of AR and FOXA1. In agreement with transcriptional changes, depleting BRG1 conferred G1 arrest.ConclusionsOur data have revealed that BRG1 has capacity to drive oncogenesis by coordinating oncogenic pathways dependent on BRG1 for proliferation, cell cycle progression and DNA replication.

scholarly journals Overexpression 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 ◽  
Cell Cycle Progression ◽  
Colony Growth ◽  
Normal Tissues ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Abstract Background: Pancreatic cancer is a malignant tumor with high lethality. Acidic nuclear phosphoprotein 32 family member E (ANP32E) is a specific H2A.Z chaperone. The role of ANP32E in pancreatic cancer is poorly understood. This study aimed to investigate the clinical relevance and function of ANP32E in pancreatic cancer.Methods: The expression of ANP32E in 179 pancreatic cancer tissues and 171 normal tissues, and its correlation with patients’ survival were analyzed from the TCGA database. ANP32E was overexpressed and silenced using lentivirus. siRNA was used to knock down β-catenin. CCK8, colony formation, cell cycle detection and Transwell assays were performed to determine cell proliferation and migration. qRT-PCR and Western blot were conducted to detect mRNA and protein expression.Results: ANP32E was an oncogene in pancreatic cancer. ANP32E was up-regulated in pancreatic cancer tissues and cells. Up-regulation of ANP32E predicted poor survival in patients. Lentivirus-mediated knockdown of ANP32E suppressed the proliferation, colony growth and migration of PANC1 and MIA cells. By contrast, ANP32E overexpression promoted the proliferation and migration capacity of the cells. In addition, ANP32E overexpression 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 reveal that ANP32E functions as an oncogene in pancreatic cancer via activating β-catenin.

scholarly journals Acetylation of Mammalian ADA3 Is Required for Its Functional Roles in Histone Acetylation and Cell Proliferation

2016 ◽  
Vol 36 (19) ◽  
pp. 2487-2502 ◽  
Author(s):  
Shakur Mohibi ◽  
Shashank Srivastava ◽  
Aditya Bele ◽  
Sameer Mirza ◽  
Hamid Band ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Histone Acetylation ◽  
Cell Cycle Progression ◽  
Site Directed Mutagenesis ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Functional Roles ◽  
A Cell ◽  
Cycle Dependent

Alteration/deficiency in activation 3 (ADA3) is an essential component of specific histone acetyltransferase (HAT) complexes. We have previously shown that ADA3 is required for establishing global histone acetylation patterns and for normal cell cycle progression (S. Mohibi et al., J Biol Chem 287:29442–29456, 2012,http://dx.doi.org/10.1074/jbc.M112.378901). Here, we report that these functional roles of ADA3 require its acetylation. We show that ADA3 acetylation, which is dynamically regulated in a cell cycle-dependent manner, reflects a balance of coordinated actions of its associated HATs, GCN5, PCAF, and p300, and a new partner that we define, the deacetylase SIRT1. We use mass spectrometry and site-directed mutagenesis to identify major sites of ADA3 acetylated by GCN5 and p300. Acetylation-defective mutants are capable of interacting with HATs and other components of HAT complexes but are deficient in their ability to restore ADA3-dependent global or locus-specific histone acetylation marks and cell proliferation inAda3-deleted murine embryonic fibroblasts (MEFs). Given the key importance of ADA3-containing HAT complexes in the regulation of various biological processes, including the cell cycle, our study presents a novel mechanism to regulate the function of these complexes through dynamic ADA3 acetylation.

scholarly journals ARHGAP24 inhibits cell proliferation and cell cycle progression and induces apoptosis of lung cancer via a STAT6-WWP2-p27 axis

2019 ◽  
Vol 41 (5) ◽  
pp. 711-721 ◽  
Author(s):  
Lei Wang ◽  
Saie Shen ◽  
Haibo Xiao ◽  
Fangbao Ding ◽  
Mingsong Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cell Apoptosis ◽  
Cell Cycle Progression ◽  
Rho Gtpase ◽  
The Cancer Genome Atlas ◽  
G1 Phase ◽  
Cycle Progression

Abstract Rho GTPase-activating proteins (RhoGAPs) have been reported to be of great importance in the initiation and development of many different cancers. However, their biological roles and regulatory mechanisms in lung cancer development and progression are poorly defined. Real-time PCR or western blotting analysis was used to detect Rho GTPase-activating protein 24 (ARHGAP24), WWP2, p27, p-STAT6 and STAT6 expression levels as well as the activity of RhoA and Rac1 in lung cancer. Cell proliferation, apoptosis and cell cycle were measured by CCK-8 and flow cytometry analysis. Tumor growth of lung cancer cells was measured using a nude mouse xenograft experiment model in vivo. The correlation between WWP2 and p27 was measured by co-immunoprecipitation and ubiquitination analysis. We found that ARHGAP24 expression was lower in lung cancer tissues collected from the The Cancer Genome Atlas and independent hospital database. Overexpression of ARHGAP24 significantly suppressed cell proliferation and the activity of RhoA and Rac1, induced cell apoptosis and arrested cell cycle at the G0–G1 phase. ARHGAP24 overexpression also inhibited tumor growth in nude mice, whereas knockdown of ARHGAP24 significantly promoted cell proliferation and WWP2 expression and inhibited cell cycle arrest at G1 phase through activating STAT6 signaling. ARHGAP24 overexpression inhibited WWP2 overexpression-induced cell proliferation, cell cycle progression and the decreased p27 expression. Moreover, WWP2 was found interacted with p27, and WWP2 overexpression promoted the ubiquitination of p27. In conclusion, our findings suggest that ARHGAP24 inhibits cell proliferation and cell cycle progression and induces cell apoptosis of lung cancer via a STAT6-WWP2-p27 axis.

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