scholarly journals Long Noncoding RNA TUG1/miR-29c Axis Affects Cell Proliferation, Invasion, and Migration in Human Pancreatic Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yebin Lu ◽  
Ling Tang ◽  
Zhipeng Zhang ◽  
Shengyu Li ◽  
Shuai Liang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Matrix Metalloproteinase ◽  
Human Pancreatic Cancer ◽  
Matrix Metalloproteinase 2 ◽  
Integrin Subunit ◽  
Normal Tissues

Given the low resection rate and chemoresistance of patients with pancreatic cancer (PC), their survival rates are typically poor. Long noncoding RNAs (lncRNAs) have recently been shown to play an important role in tumourigenesis and human cancer progression, including in PC. In this study, we aimed to investigate the role of taurine-upregulated gene 1 (TUG1) in PC. A quantitative polymerase chain reaction was used to analyse TUG1 expression in PC tissues and peritumoural normal tissues. TUG1 was overexpressed in PC tissues compared with that in peritumoural normal tissues, and the high expression of TUG1 was associated with the poor prognosis of patients with PC. Furthermore, TUG1 knockdown significantly inhibited the proliferation and invasion of PC cells both in vitro and in vivo, while overexpression TUG1 promoted tumour cell proliferation, migration, and invasion. TUG1 directly targeted miR-29c, a tumour suppressor in several cancers. TUG1 knockdown significantly increased the expression of miR-29c and subsequently induced the downregulation of integrin subunit beta 1 (ITGB1), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9). The downregulation of miR-29c abolished the TUG1 knockdown-mediated inhibition of tumour growth in vitro and in vivo, whereas the upregulation of miR-29c enhanced the effects of TUG1 knockdown on PC cells. In conclusion, we demonstrate for the first time the oncogenic role of TUG1 in PC. The downregulation of TUG1 significantly inhibited the growth and migratory ability of PC cells in vitro and in vivo by targeting miR-29c. Our study provides a novel potential diagnostic biomarker and therapeutic target for PC.

scholarly journals KIF4A Regulates the Progression of Pancreatic Ductal Adenocarcinoma through Proliferation and Invasion

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jing Chen ◽  
Cui-Cui Zhao ◽  
Fei-Ran Chen ◽  
Guo-Wei Feng ◽  
Fei Luo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
High Expression ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion

Background. Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). Methods. We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. Results. We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed ( P < 0.05 ) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) ( P < 0.05 , respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control ( P < 0.05 , respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. Conclusion. In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.

scholarly journals Dual Effects ofβ3Integrin Subunit Expression on Human Pancreatic Cancer Models

2010 ◽  
Vol 33 (5-6) ◽  
pp. 191-205 ◽  
Author(s):  
S. Marchán ◽  
S. Pérez-Torras ◽  
A. Vidal ◽  
J. Adan ◽  
F. Mitjans ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Rho Gtpases ◽  
Cell Attachment ◽  
Human Pancreatic Cancer ◽  
Cell Growth And Migration ◽  
Subunit Expression ◽  
And Migration

Background: Pancreatic cancer, the fifth leading cause of adult cancer death in Western countries, lacks early detection, and displays significant dissemination ability. Accumulating evidence shows that integrin-mediated cell attachment to the extracellular matrix induces phenotypes and signaling pathways that regulate tumor cell growth and migration.Methods: In view of these findings, we examined the role ofβ3in pancreatic cancer by generating two stableβ3-expressing pancreatic human cell lines and characterizing their behavior in vitro and in vivo.Results: Transduction ofβ3selectively augmented the functional membraneαvβ3integrin levels, as evident from the enhanced adhesion and migration abilities related to active Rho GTPases. No effects on in vitro anchorage-dependent growth, but higher anoikis were detected inβ3-overexpressing cells. Moreover, tumors expressingβ3displayed reduced growth. Interestingly, treatment of mice with anαv-blocking antibody inhibited the growth ofβ3-expressing tumors to a higher extent.Conclusion: Our results collectively support the hypothesis thatαvβ3integrin has dual actions depending on the cell environment, and provide additional evidence on the role of integrins in pancreatic cancer, which should eventually aid in improving prediction of the effects of therapies addressed to modulate integrin activities in these tumors.

scholarly journals miR-365 Suppresses Cholangiocarcinoma Cell Proliferation and Induces Apoptosis by Targeting E2F2

2018 ◽  
Vol 26 (9) ◽  
pp. 1375-1382 ◽  
Author(s):  
Lunjian Chen ◽  
Xiaorong Huang ◽  
Xinxin Chen
Keyword(s):  
Cell Proliferation ◽  
Inverse Correlation ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Cholangiocarcinoma Cell ◽  
Cellular Apoptosis ◽  
Growth Of Tumor

Cholangiocarcinoma (CCA) is one of the most malignant adenocarcinomas arising from bile duct epithelial cells. However, the molecular mechanism regulating CCA development and progression still needs to be investigated. Here we found that miR-365 was downregulated in CCA tissues compared with adjacent normal tissues. By functional experiments, we found that overexpression of miR-365 significantly inhibited CCA cell proliferation and promoted cellular apoptosis in vitro. Furthermore, administration with miR-365 markedly suppressed the growth of tumor tissues in vivo. Mechanistically, we identified E2F2 as the target gene of miR-365 in CCA cells. We found that overexpression significantly inhibited the expression of E2F2 in CCA cells, and there was an inverse correlation between the expression levels of E2F2 and miR-365 in CCA tissues. We also found that E2F2 was highly expressed in CCA tissues and cell lines. Restoration of E2F2 in miR-365-overexpressing CCA cells promoted cell viability and reduced cellular apoptosis in CCA. Collectively, our study demonstrated the essential role of miR-365 and its functional mechanism in CCA cells, which provided a new insight on the design of therapeutic targets for CCA treatment.

scholarly journals Naa10p promotes metastasis by stabilizing matrix metalloproteinase-2 protein in human osteosarcomas

2018 ◽  
Author(s):  
Ming-Hsien Chien ◽  
Wei-Jiunn Lee ◽  
Yi-Chieh Yang ◽  
Peng Tan ◽  
Ke-Fan Pan ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Complex Activity ◽  
Metastatic Osteosarcoma ◽  
Cell Invasiveness ◽  
Acetyltransferase Domain ◽  
Worse Prognosis

AbstractN-α-Acetyltransferase 10 protein (Naa10p) mediates N-terminal acetylation of nascent proteins. Oncogenic or tumor suppressive roles of Naa10p were reported in cancers. Here, we report an oncogenic role of Naa10p in promoting metastasis of osteosarcomas. HigherNAA10transcripts were observed in metastatic osteosarcoma tissues compared to non-metastatic tissues and were also correlated with a worse prognosis of patients. Knockdown and overexpression of Naa10p in osteosarcoma cells respectively led to decreased and increased cell migratory/invasive abilities. Re-expression of Naa10p, but not an enzymatically inactive mutant, relieved suppression of the invasive abilityin vitroand metastasisin vivoimposed by Naa10p-knockdown. According to protease array screening, we identified that matrix metalloproteinase (MMP)-2 was responsible for the Naa10p-induced invasive phenotype. Naa10p was directly associated with MMP-2 protein through its acetyltransferase domain and maintained MMP-2 protein stability via NatA complex activity. MMP-2 expression levels were also significantly correlated with Naa10p levels in osteosarcoma tissues. These results reveal a novel function of Naa10p in the regulation of cell invasiveness by preventing MMP-2 protein degradation that is crucial during osteosarcoma metastasis.

scholarly journals Histone methyltransferase SUV39H2 regulates cell growth and chemosensitivity in glioma via regulation of hedgehog signaling

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ran Wang ◽  
Lilin Cheng ◽  
Xi Yang ◽  
Xin Chen ◽  
Yifeng Miao ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Hedgehog Signaling ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Normal Tissues

Abstract Background Malignant glioma is one of the essentially incurable tumors with chemoresistance and tumor recurrence. As a histone methyltransferase, SUV39H2 can trimethylate H3K9. SUV39H2 is highly expressed in many types of human tumors, while the function of SUV39H2 in the development and progression of glioma has never been elucidated. Methods RT-qPCR and IHC were used to test SUV39H2 levels in glioma tissues and paired normal tissues. The clinical relevance of SUV39H2 in glioma was analyzed in a public database. Colony formation assays, CCK-8 assays, and flow cytometry were conducted to explore the role of SUV39H2 in the growth of glioma cells in vitro. A cell line-derived xenograft model was applied to explore SUV39H2’s role in U251 cell proliferation in vivo. Sphere formation assays, RT-qPCR, flow cytometry, and IF were conducted to illustrate the role of SUV39H2 in the stemness and chemosensitivity of glioma. Luciferase reporter assays and WB were applied to determine the function of SUV39H2 in Hh signaling. Results SUV39H2 was highly expressed in glioma tissues relative to normal tissues. SUV39H2 knockdown inhibited cell proliferation and stemness and promoted the chemosensitivity of glioma cells in vitro. In addition, SUV39H2 knockdown also significantly inhibited glioma cell growth in vivo. Moreover, we further uncovered that SUV39H2 regulated hedgehog signaling by repressing HHIP expression. Conclusions Our findings delineate the role of SUV39H2 in glioma cell growth and chemosensitivity as a pivotal regulator of the hedgehog signaling pathway and may support SUV39H2 as a potential target for diagnosis and therapy in glioma management.

scholarly journals Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Bingyi Wang ◽  
Yan Xu ◽  
Yuhua Wei ◽  
Lixin Lv ◽  
Nanbin Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Human Mesenchymal Stem Cells ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Luciferase Assay ◽  
Human Pancreatic Cancer

BackgroundThis study aimed to explore the regulatory mechanism of hsa-miR-143-3p and lncRNA RP11-363N22.3–functioning upstream of KRAS–in exosomes derived from human mesenchymal stem cells (hMSCs) in pancreatic cancer.MethodsWestern blotting and quantitative PCR were used to determine gene expression. In vitro, cell proliferation, apoptosis, and cell cycle and invasion were evaluated using CCK-8 assay, flow cytometry, and transwell assays, respectively. In vivo, the effect of hsa-miR143-3p was investigated using a tumorigenesis test in nude mice. The association between hsa-miR-143-3p and lncRNA RP11-363N22.3 was investigated using the dual-luciferase assay.Resultshsa-miR-143-3p expression significantly increased in hMSC exosomes than in those in human pancreatic cancer cell line (CFPAC-1) exosomes. In vitro, compared to the MOCK (CFPAC-1 only) group, cell proliferation and invasion were inhibited and apoptosis was induced in the inhibitor NC (CFPAC-1 + MSC-hsa-miR-3p inhibitor NC) group, while these changes were reversed in the inhibitor (CFPAC-1 + MSC-hsa-miR-3p inhibitor) group. The expression of lncRNA RP11-363N22.3 and genes related to miR-143 significantly decreased in the inhibitor NC group compared to the MOCK group, and increased in the inhibitor group compared to inhibitor NC group. A targeted combinatorial effect was observed between lncRNA RP11-363N22.3 and hsa-miR-143-3p. In vivo, the tumor volume of the mimics (CFPAC-1 + MSC-hsa-miR-143-3p mimics) group was smaller than that of the mimics NC (CFPAC-1 + MSC-hsa-miR-143-3p mimics NC) and MOCK groups. H&amp;E staining showed that there were no obvious pathological changes in MOCK and mimic NC groups, while cell necrosis was seen in some regions in mimic groups.Conclusionhsa-miR-143-3p may promote apoptosis and suppress cell growth and invasion in pancreatic cancer.

In Vitro and In Vivo Antitumor Efficacy of Docetaxel and Sorafenib Combination in Human Pancreatic Cancer Cells

2010 ◽  
Vol 999 (999) ◽  
pp. 1-11
Author(s):  
P. Ulivi ◽  
C. Arienti ◽  
W. Zoli ◽  
M. Scarsella ◽  
S. Carloni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Antitumor Efficacy ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

scholarly journals Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001364
Author(s):  
Yan Zhang ◽  
Hui Yang ◽  
Jun Zhao ◽  
Ping Wan ◽  
Ye Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Metabolism ◽  
Vital Role ◽  
Methionine Metabolism ◽  
Promoter Regions ◽  
Normal Tissues ◽  
Methionine Cycle

BackgroundThe activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.MethodsMonocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed.ResultsTAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions.ConclusionsOur data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.

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