scholarly journals LncRNA TP73-AS1 sponges miR-141-3p to promote the migration and invasion of pancreatic cancer cells through the up-regulation of BDH2

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Xian-Ping Cui ◽  
Chuan-Xi Wang ◽  
Zhi-Yi Wang ◽  
Jian Li ◽  
Ya-Wen Tan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Human Pancreatic Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Pancreatic Cancer Cells ◽  
Candidate Target ◽  
Direct Target

Abstract LncRNA TP73 antisense RNA 1T (TP73-AS1) plays an important role in human malignancies. However, the levels of TP73-AS1 and its functional mechanisms in pancreatic cancer metastasis remain unknown, and the clinical significance of TP73-AS1 in human pancreatic cancer is also unclear. In the present study, the levels of TP73-AS1 and its candidate target miR-141 in pancreatic cancer and adjacent normal tissue were detected using qRT-PCR. The association between TP73-AS1 levels and the clinicopathologic characteristics of pancreatic cancer patients were analyzed. The relationship between TP73-AS1 and miR-141, and miR-141 and its candidate target 3-hydroxybutyrate dehydrogenase type 2 (BDH2) was confirmed using dual-luciferase reporter assays. TP73-AS1 and/or miR-141 were knocked down using siRNA or an inhibitor in pancreatic cancer cells and cell migration and invasion then examined. The results showed that TP73-AS1 was up-regulated in pancreatic cancer tissue and cell lines. High levels of TP73-AS1 were correlated with poor clinicopathological characteristics and shorter overall survival. MiR-141 was a direct target for TP73-AS1, while BDH2 was a direct target for miR-141. The knockdown of TP73-AS1 significantly inhibited the migration and invasion of pancreatic cancer cells, while the miR-141 inhibitor significantly restored the migration and invasion. Therefore, TP73-AS1 positively regulated BDH2 expression by sponging miR-141. These findings suggest that TP73-AS1 serves as an oncogene and promotes the metastasis of pancreatic cancer. Moreover, TP73-AS1 could serve as a predictor and a potential drug biotarget for pancreatic cancer.

scholarly journals Identification of phosphoenolpyruvate carboxykinase 1 as a potential therapeutic target for pancreatic cancer

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Xiao-ren Zhu ◽  
Shi-qing Peng ◽  
Le Wang ◽  
Xiao-yu Chen ◽  
Chun-xia Feng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Human Pancreatic Cancer ◽  
Migration And Invasion ◽  
Potential Therapeutic Target ◽  
Protein Levels ◽  
Pancreatic Cancer Cells

AbstractPancreatic cancer is the third leading cause of cancer-related mortalities and is characterized by rapid disease progression. Identification of novel therapeutic targets for this devastating disease is important. Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme of gluconeogenesis. The current study tested the expression and potential functions of PCK1 in pancreatic cancer. We show that PCK1 mRNA and protein levels are significantly elevated in human pancreatic cancer tissues and cells. In established and primary pancreatic cancer cells, PCK1 silencing (by shRNA) or CRISPR/Cas9-induced PCK1 knockout potently inhibited cell growth, proliferation, migration and invasion, and induced robust apoptosis activation. Conversely, ectopic overexpression of PCK1 in pancreatic cancer cells accelerated cell proliferation and migration. RNA-seq analyzing of differentially expressed genes (DEGs) in PCK1-silenced pancreatic cancer cells implied that DEGs were enriched in the PI3K-Akt-mTOR cascade. In pancreatic cancer cells, Akt-mTOR activation was largely inhibited by PCK1 shRNA, but was augmented after ectopic PCK1 overexpression. In vivo, the growth of PCK1 shRNA-bearing PANC-1 xenografts was largely inhibited in nude mice. Akt-mTOR activation was suppressed in PCK1 shRNA-expressing PANC-1 xenograft tissues. Collectively, PCK1 is a potential therapeutic target for pancreatic cancer.

MicroRNA-1179 inhibits the proliferation, migration and invasion of human pancreatic cancer cells by targeting E2F5

2018 ◽  
Vol 291 ◽  
pp. 65-71 ◽  
Author(s):  
Chengjie Lin ◽  
Zhigao Hu ◽  
Guandou Yuan ◽  
Huizhao Su ◽  
Yonglian Zeng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Migration And Invasion ◽  
Pancreatic Cancer Cells

scholarly journals Propofol Mediates Pancreatic Cancer Cell Activity Through the Repression of ADAM8 via SP1

2021 ◽  
Author(s):  
Yutong Gao ◽  
Yu Zhou ◽  
Chunlin Wang ◽  
Klarke Sample ◽  
Xiangdi Yu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cell Activity ◽  
Pancreatic Cancer Cell Line ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Physical Interaction ◽  
Pancreatic Cancer Cells

Abstract Background Propofol is a commonly used anesthetic with controversial effects on cancer cells. A growing number of studies have demonstrated that low concentrations of propofol are associated with tumor suppression and when used as an intravenous anesthesia improved recurrence-free survival rates for many cancers, but deeper insights into its underlying mechanism are needed. Methods The study detailed herein focuses upon the effect of propofol on pancreatic cancer cells and the mechanism by which propofol reduces ADAM8 expression. The ability of propofol to impact the proliferation, migration and cell cycle of a pancreatic cancer cell line was assessed in vitro. This was mechanistically explored following the identification of SP1 binding sites within ADAM8, which enabled the regulatory effects of SP1 on ADAM8 following propofol treatment to be further explored. Results This study was able to show that propofol significantly inhibited the proliferation, migration and invasion of pancreatic cancer cells and decreased the percentage of cells in S-phase. Propofol treatment was also shown to repress ADAM8 and SP1 expression, but was unable to affect ADAM8 expression following knockdown of SP1. Moreover, a direct physical interaction between SP1 and ADAM8 was verified using Co-immunoprecipitation and dual-luciferase reporter assays. Conclusion These results suggest that propofol represses pathological biological behaviors associated with pancreatic cancer cells through the suppression of SP1, which in turn results in lower ADAM8 mRNA expression and protein levels.

In Vitro Inhibition of Piper nigrum and Piperine on Growth, Migration, and Invasion of PANC-1 Human Pancreatic Cancer Cells

2021 ◽  
Vol 16 (11) ◽  
pp. 1934578X2110576
Author(s):  
Ji Hye Jeong ◽  
Jae-Ha Ryu ◽  
Hwa Jin Lee
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cyclin B1 ◽  
Human Pancreatic Cancer ◽  
Major Constituent ◽  
Piper Nigrum ◽  
Migration And Invasion ◽  
Cell Cycle Regulators ◽  
Pancreatic Cancer Cells

Several dietary and medicinal herbs have been shown to be effective in the treatment and prevention of cancer. Although Piper nigrum has been shown to have anti-cancer activities against various cancer cells, its anti-pancreatic cancer properties have not been reported. In the present study, P. nigrum extract (PNE) inhibited proliferation of PANC-1 human pancreatic cancer cells. Flow cytometry showed G0/G1 arrest caused by PNE in PANC-1 cells. In addition, Western blot analysis showed that PNE suppressed the protein levels of cell cycle regulators such as cyclin B1, cyclin D1, survivin, and Forkhead box M1 (FoxM1). These findings suggested that the inhibitory activity of PNE against the growth of PANC-1 cells was correlated with cell cycle arrest and repression of cell cycle regulators. Wound healing and trans-well assays showed that PNE suppressed migration and invasion of PANC-1 cells. Piperine, a major alkaloid of Piper nigrum, was identified as the main component of PNE by HPLC analysis. Piperine also attenuated the cell growth, migration, and invasion of PANC-1 cells, suggesting its contribution to the anti-pancreatic cancer effects of PNE. These results demonstrate that PNE and its major constituent, piperine, have anti-pancreatic cancer properties such as growth-inhibition, anti-migration, and anti-invasion of cancer cells.

Ceramide 1-phosphate regulates cell migration and invasion of human pancreatic cancer cells

2016 ◽  
Vol 102 ◽  
pp. 107-119 ◽  
Author(s):  
Io-Guané Rivera ◽  
Marta Ordoñez ◽  
Natalia Presa ◽  
Patricia Gangoiti ◽  
Ana Gomez-Larrauri ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Pancreatic Cancer Cells ◽  
Ceramide 1

scholarly journals Elevated expression of nuclear receptor-binding SET domain 3 promotes pancreatic cancer cell growth

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yihui Sun ◽  
Jiaming Xie ◽  
Shang Cai ◽  
Qian Wang ◽  
Zhenyu Feng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Nuclear Receptor ◽  
Receptor Binding ◽  
Ectopic Expression ◽  
Human Pancreatic Cancer ◽  
Migration And Invasion ◽  
Set Domain ◽  
Pancreatic Cancer Cells ◽  
Domain 3

AbstractThe nuclear receptor-binding SET domain 3 (NSD3) catalyzes methylation of histone H3 at lysine 36 (H3K36), and promotes malignant transformation and progression of human cancer. Its expression, potential functions and underlying mechanisms in pancreatic cancer are studied. Bioinformatics studies and results from local human tissues show that NSD3 is upregulated in human pancreatic cancer tissues, which is correlated with poor overall survival. In primary and established pancreatic cancer cells, NSD3 silencing (by shRNAs) or CRISPR/Cas9-induced NSD3 knockout potently inhibited cell proliferation, migration and invasion, while provoking cell cycle arrest and apoptosis. Conversely, ectopic expression of NSD3-T1232A mutation significantly accelerated proliferation, migration, and invasion of pancreatic cancer cells. H3K36 dimethylation, expression of NSD3-dependent genes (Prkaa2, Myc, Irgm1, Adam12, and Notch3), and mTOR activation (S6K1 phosphorylation) were largely inhibited by NSD3 silencing or knockout. In vivo, intratumoral injection of adeno-associated virus (AAV)-packed NSD3 shRNA potently inhibited pancreatic cancer xenograft growth in nude mice. These results suggest that elevated NSD3 could be an important driver for the malignant progression of pancreatic cancer.

scholarly journals E3 Ubiquitin Ligase UBR5 Promotes the Metastasis of Pancreatic Cancer via Destabilizing F-Actin Capping Protein CAPZA1

2021 ◽  
Vol 11 ◽  
Author(s):  
Jin Li ◽  
Wei Zhang ◽  
Jian Gao ◽  
Min Du ◽  
Huimin Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Ubiquitin Ligase ◽  
Cancer Metastasis ◽  
E3 Ubiquitin Ligase ◽  
Migration And Invasion ◽  
Capping Protein ◽  
Pancreatic Cancer Cells ◽  
Actin Capping Protein ◽  
Actin Capping

The ubiquitin-proteasome system (UPS) is a regulated mechanism of intracellular protein degradation and turnover, and its dysfunction is associated with various diseases including cancer. UBR5, an E3 ubiquitin ligase, is emerging as an important regulator of the UPS in cancers, but its role in pancreatic cancer is poorly understood. Here, we show that UBR5 is significantly upregulated in pancreatic cancer tissues. High UBR5 expression is correlated with increased lymph node metastasis and poor survival of patients. The loss-of-function and gain-of-function studies demonstrated that UBR5 substantially enhanced the in vitro migratory and invasive ability of pancreatic cancer cells. UBR5 knockdown also markedly inhibited in vivo cancer metastasis in the liver metastatic model of pancreatic cancer in nude mice, suggesting UBR5 as a potent metastatic promoter in pancreatic cancer. Furthermore, using co-immunoprecipitation combined with mass spectrometry analyses, CAPZA1, a member of F-actin capping protein α subunit family, was identified as a novel substrate of UBR5. UBR5 overexpression could promote the degradation of CAPZA1 via the UPS and induce the accumulation of F-actin, which has been described as an essential molecular event during the process of CAPZA1 deficiency-induced cancer cells migration and invasion. UBR5 knockdown significantly increased the intracellular level of CAPZA1 and CAPZA1 downregulation largely reversed the UBR5 knockdown-induced suppression of cell migration and invasion in pancreatic cancer cells. Collectively, our findings unveil UBR5 as a novel and critical regulator of pancreatic cancer metastasis and highlight the potential for UBR5-CAPZA1 axis as a therapeutic target for preventing metastasis in pancreatic cancer patients, especially in those with increased UBR5 expression.

scholarly journals STAT1-mediated inhibition of FOXM1 enhances gemcitabine sensitivity in pancreatic cancer

2019 ◽  
Vol 133 (5) ◽  
pp. 645-663 ◽  
Author(s):  
Chao Liu ◽  
Jiaqi Shi ◽  
Qingwei Li ◽  
Zhiwei Li ◽  
Changjie Lou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Immunohistochemical Analysis ◽  
Human Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Luciferase Reporter ◽  
Pancreatic Cancer Cells ◽  
Foxm1 Expression

Abstract Forkhead box protein M1 (FOXM1) was identified as an oncogenic transcription factor and master regulator of tumor progression and metastasis. FOXM1 expression often correlates with poor prognosis and chemotherapy resistance. In the present study, we investigated the association of FOXM1 expression and chemoresistance in pancreatic cancer. Elevated FOXM1 protein levels were associated with gemcitabine chemoresistance in patients with pancreatic cancer. In gemcitabine resistance cell line models of pancreatic cancer, FOXM1 expression increased, which induced gemcitabine chemoresistance in vitro. In pancreatic cancer cells treated with gemcitabine, FOXM1 affected nuclear factor κB (NF-κB) signaling activity. Immunohistochemical analysis demonstrated a negative association of FOXM1 expression and the level of phosphorylated signal transducer and activator of transcription 1 (pSTAT1) in human pancreatic cancer tissues. Dual-luciferase reporter assays and chromatin-immunoprecipitation assays demonstrated that pSTAT1 directly binds to the FOXM1 promoter to down-regulate its transcription. Interferon γ (IFNγ) promoted gemcitabine-induced cell apoptosis and inhibited cell proliferation in vitro and in vivo by FOXM1 inhibition. These data suggested that FOXM1 enhances chemoresistance to gemcitabine in pancreatic cancer. IFNγ could be used to down-regulate the expression of FOXM1 through STAT1 phosphorylation, thereby increasing the sensitivity of pancreatic cancer cells to gemcitabine. These studies suggested the sensitization by IFNγ in pancreatic ductal adenocarcinoma (PDAC) chemotherapy, which requires further clinical studies.

scholarly journals MiR-203a-3p Inhibits Pancreatic Cancer Cell Proliferation, EMT, and Apoptosis by Regulating SLUG

2020 ◽  
Vol 19 ◽  
pp. 153303381989872 ◽  
Author(s):  
Ning An ◽  
Bo Zheng
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Transition Process ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Messenger Rnas ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
Cancer Tissues

Objective: The aim of the present research is to study the roles of miR-203a-3p on cell proliferation, migration, invasion, and epithelial–mesenchymal transition in pancreatic cancer. Methods: Transcription profiles were acquired from Gene Expression Omnibus database, which was used to screen out the differentially expressed microRNAs and messenger RNAs in pancreatic cancer. Pancreatic cancer tissues were used to verify the bioinformatics results by quantitative real-time polymerase chain reaction. The relationship between miR-203a-3p and SLUG was examined by TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation. The Cell Counting Kit-8, wound healing, and transwell assays were conducted to investigate the proliferation, migration, and invasion capability of pancreatic cancer cells, respectively. The expression of epithelial–mesenchymal transition–related proteins was determined by the Western blot assay. Xenograft assay was performed to verify findings from in vitro assays. Results: Bioinformatic analysis found that a total of 113 microRNAs and 1749 messenger RNAs expressed differentially in pancreatic cancer tissues. Among these microRNAs, the expression of miR-203a-3p was significantly decreased in both pancreatic cancer tissues and cells. On the other hand, the SLUG expression was remarkably upregulated in pancreatic cancer tissues and cells in comparison with normal tissues and cells. Moreover, TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation revealed that SLUG was a target of miR-203a-3p. The upregulation of miR-203a-3p expression inhibited the proliferation, migration, and invasion ability of pancreatic cancer cells by suppressing the epithelial–mesenchymal transition process via sponging SLUG. Conclusion: These findings indicate that downregulation of miR-203a-3p in pancreatic cancer cells leads to high expression of SLUG, which promotes epithelial–mesenchymal transition process and induces cancer progression.

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