scholarly journals Correlated high expression of FXR and Sp1 in cancer cells confers a poor prognosis for pancreatic cancer: A study based on TCGA and tissue microarray

Oncotarget ◽  
2017 ◽  
Vol 8 (20) ◽  
pp. 33265-33275 ◽  
Author(s):  
Hai Hu ◽  
Lei-Lei Wu ◽  
Ting Han ◽  
Meng Zhuo ◽  
Wang Lei ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Tissue Microarray ◽  
Poor Prognosis ◽  
High Expression

Sex Determining Region Y Box 9 Induces Chemoresistance in Pancreatic Cancer Cells by Induction of Putative Cancer Stem Cell Characteristics and Its High Expression Predicts Poor Prognosis

Pancreas ◽  
2017 ◽  
Vol 46 (10) ◽  
pp. 1296-1304 ◽  
Author(s):  
Taku Higashihara ◽  
Hideyuki Yoshitomi ◽  
Yasuyuki Nakata ◽  
Shingo Kagawa ◽  
Shigetsugu Takano ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
High Expression ◽  
Pancreatic Cancer Cells

Abstract A35: SOX9 induces chemo-resistance in pancreatic cancer cells and its high expression predicts poor prognosis

2016 ◽  
Author(s):  
Shingo Kagawa ◽  
Taku Higasihara ◽  
Hideyuki Yoshitomi ◽  
Shigetsugu Takano ◽  
Hiroaki Shimizu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
High Expression ◽  
Pancreatic Cancer Cells

734 A novel NQO1 specific anti-tumor agent, SBSC-S3001, selectively regresses the growth of tumors with high NQO1 expression

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A778-A778
Author(s):  
Minhyuk Yun ◽  
Goo-Young Kim ◽  
Sang Woo Jo ◽  
Changhoon In ◽  
Gyu-Young Moon ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
High Expression ◽  
List Type ◽  
Dependent Manner ◽  
Breast Cancers ◽  
Quinone Oxidoreductase ◽  
Key Enzymes

BackgroundNAD(P)H-quinone oxidoreductase 1 (NQO1) is a cytosolic two-electron oxidoreductase overexpressed in many types of cancers, including breast cancer, pancreatic cancer, colorectal cancer, cholangiocarcinoma, uterine cervical cancer, melanoma, and lung cancer.1Up-regulation of NQO1 protects cells from oxidative stress and various cytotoxic quinones and is associated with late clinical stage, poor prognosis and lymph node metastasis.2 3 NQO1 increases stability of HIF-1α protein, which has been implicated in survival, proliferation, and malignance of cancer.1 Therefore, accumulating evidences suggest NQO1 as a promising therapeutic target for cancer. Accordingly, we have characterized the effect of a novel synthetic NQO1 substrate SBSC-S3001, and demonstrated its selective cytotoxic effects in cancer cells with high expression of NQO1.MethodsIn vitro cytotoxicity was determined by sulforhodamine B (SRB) assay in cancer cells with high NQO1 expression and CRISPR-mediated NQO1 knockout cells. The effect of SBSC-S3001 on the energy metabolism pathway was evaluated by western blot analysis of metabolism associated proteins from NQO1-overexpressed cancer cells treated with the compound for 24 hours. In vivo anti-tumor activity was evaluated in MC38 syngeneic and DLD-1 orthotopic mice models.ResultsSBSC-S3001 exhibited selective cytotoxicity in cancer cells with high expression of NQO1 in a dose-dependent manner. The cytotoxicity was observed in both normoxia and hypoxia conditions, correlating with the energy metabolism, mitochondrial biogenesis, and cancer proliferative pathways. Also, stronger cytotoxicity was observed in NQO1-overexpressed cancer cells treated with SBSC-S3001 compared to beta-lapachone and analogue treatment.4 When evaluated in vivo, SBSC-S3001 effectively inhibited the growth of syngeneic and orthotopic tumors when administered as a monotherapy. SBSC-S3001 treatment associated with reduction in key enzymes of the glycolytic pathway (LDHa and GAPDH) and HIF-1α and increase in levels of mitochondrial oxidative phosphorylation (OXPHOS) complex.ConclusionsTreatment of SBSC-S3001, a novel, NQO1-specific substrate reduces HIF-1α and key enzymes associated with glycolysis and suppresses the growth of tumors overexpressing NQO1. Further characterization of SBSC-S3001 as a novel metabolic anti-cancer agent for cancers with NQO1 overexpression is warranted.Ethics ApprovalThe study was approved by Samyang Biopharmaceuticals Institution’s Ethics Board, approval number SYAU2031.ReferencesOh ET, Kim JW, Kim JMet. al., NQO1 inhibits proteasome-mediated degradation of HIF-1α. Nat Commun 2016; 14:13593.Ma, Y. et al. NQO1 overexpression is associated with poor prognosis in squamous cell carcinoma of the uterine cervix. BMC Cancer 2014;14: 414Yang, Y. et al. Clinical implications of high NQO1 expression in breast cancers. J. Exp. Clin. Cancer Res 2014;33:144.Yang Y, Zhou X, Xu M, et al., β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers. Sci Rep 2017;7:2681.

A genetic variant conferred high expression of CAV2 promotes pancreatic cancer progression and associates with poor prognosis

2021 ◽  
Vol 151 ◽  
pp. 94-105
Author(s):  
Ying Zhu ◽  
Jianbo Tian ◽  
Xiating Peng ◽  
Xiaoyang Wang ◽  
Nan Yang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Genetic Variant ◽  
High Expression

Abstract 1766: High expression of ARHGEF2 is associated with poor prognosis via c-Myc signaling in patients with pancreatic cancer

2019 ◽  
Author(s):  
Yosuke Nakao ◽  
Shigeki Nakagawa ◽  
Yo-ichi Yamashita ◽  
Rumi Itoyama ◽  
Toshihiko Yusa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
High Expression

scholarly journals DNA-Methylation-Caused Downregulation of miR-30 Contributes to the High Expression of XPO1 and the Aggressive Growth of Tumors in Pancreatic Ductal Adenocarcinoma

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1101 ◽  
Author(s):  
Asfar S. Azmi ◽  
Yiwei Li ◽  
Amro Aboukameel ◽  
Irfana Muqbil ◽  
Philip A. Philip ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Nuclear Export ◽  
The United States ◽  
High Expression ◽  
Ductal Adenocarcinoma ◽  
Multiple Tumor ◽  
Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma is one of the most aggressive cancers, with high mortality in the United States. One of the important signal transduction proteins involved in the regulation of pancreatic cancer’s aggressive progression is the nuclear export protein (XPO1). High expression of XPO1 has been found in pancreatic, lung, breast and other cancers and lymphomas with a poor prognosis of patients with tumors and high proliferative activity of cancer cells. Because XPO1 exports multiple tumor suppressor proteins simultaneously from the nucleus, the inhibition of XPO1 may retain multiple tumor suppressors in the nucleus, resulting in the suppression of cell proliferation and the induction of apoptosis in tumors. In this study, we found that the high expression of XPO1 in pancreatic cancer cells could be, in part, due to the methylation of the miR-30 gene, leading to the low expression level of the miR-30 family. By co-transfection of the XPO1 3′-UTR-Luc target vector with miR-30 mimic, we found that XPO1 is a direct target of the miR-30 family. We also observed that the enforced expression of the miR-30 family inhibited the expression of XPO1, resulting in the suppression of pancreatic cancer growth both in vitro and in vivo. These findings could help to design a novel therapeutic strategy for the treatment of pancreatic cancer by introducing miR-30 into cancer cells.

MicroRNA-296-5p Promotes Cell Invasion and Drug Resistance by Targeting Bcl2-Related Ovarian Killer, Leading to a Poor Prognosis in Pancreatic Cancer

Digestion ◽  
2019 ◽  
Vol 101 (6) ◽  
pp. 794-806 ◽  
Author(s):  
Jun Okazaki ◽  
Toshihito Tanahashi ◽  
Yasushi Sato ◽  
Jinsei Miyoshi ◽  
Tadahiko Nakagawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Poor Prognosis ◽  
Cancer Cell Lines ◽  
Pancreatic Cancer Cells ◽  
Cancer Tissues

<b><i>Background/Aims:</i></b> Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive invasion, early metastasis, and resistance to chemotherapy, leading to a poor prognosis. To clarify the molecular mechanism of these malignant characteristics, we performed a genome-wide microRNA (miRNA) array analysis utilizing micro-cancer tissues from patients with unresectable PDAC (stage IV), obtained by endoscopic ultrasound-fine needle aspiration (EUS-FNA). <b><i>Methods:</i></b> The expression profiles of 2,042 miRNAs were determined using micro-cancer tissues from 13 patients with unresectable PDAC obtained by EUS-FNA. The relationship between individual miRNA levels and overall survival (OS) was analyzed. Possible target genes for miRNAs were bioinformatically analyzed using the online database miRDB. Pancreatic cancer cell lines PANC-1, MIA PaCa-2, and PK-8 were transfected with miRNA mimic or small interfering RNA, and cell invasion, epithelial-mesenchymal transition (EMT), and apoptosis markers were examined. miRNA and mRNA expressions were examined by quantitative polymerase chain reaction. <b><i>Results:</i></b> Of 2,042 miRNAs, the 10 that exhibited the lowest correlation coefficient (<i>p</i> ≤ 0.005) between miRNA expression level and OS among the patients were identified. The miRDB and expression analysis in cancer cell lines for the 10 miRNAs identified miR-296-5p and miR-1207-5p as biomarkers predictive of shorter survival (<i>p</i> &#x3c; 0.0005). Bioinformative target gene analysis and transfection experiments with miRNA mimics showed that <i>Bcl2-related</i> <i>ovarian</i> <i>killer</i> (<i>BOK</i>), a pro-apoptotic gene, is a target for miR296-5p in pancreatic cancer cells; transfection of miR-296-5p mimic into PANC-1, MIA PaCa-2, and PK-8 cells resulted in significant suppression of <i>BOK</i> mRNA and protein expression. These transfectants showed significantly higher invasion capability compared with control cells, and knock down of <i>BOK</i> in pancreatic cancer cells similarly enhanced invasion capability. Transfectants of miR-296-5p mimic also exhibited aberrant expression of EMT markers, including vimentin and N-cadherin. Moreover, these transfectants showed a significantly lower apoptosis rate in response to 5-fluorouracil and gemcitabine with a decrease of <i>BOK</i> expression, suggesting a role of miR-296-5p in drug resistance. <b><i>Conclusion:</i></b> These results suggest that miR-296-5p is a useful biomarker for a poor prognosis in patients with PDAC, and that the miR-296-5p/BOK signaling axis plays an important role in cell invasion, drug resistance, and EMT in PDACs.

scholarly journals Long noncoding RNA GSTM3TV2 upregulates LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance in pancreatic cancer

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Guangbing Xiong ◽  
Chang Liu ◽  
Gang Yang ◽  
Mengyu Feng ◽  
Jianwei Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Reference Sequence ◽  
Gemcitabine Resistance ◽  
Cerna Network ◽  
Pancreatic Cancer Cells

Abstract Background Chemoresistance is one of the main causes of poor prognosis in pancreatic cancer patients. Understanding the mechanisms implicated in chemoresistance of pancreatic cancer is critical to improving patient outcomes. Recent evidences indicate that the long noncoding RNAs (lncRNAs) are involving in chemoresistance of pancreatic cancer. However, the mechanisms of lncRNAs contribute to resistance in pancreatic cancer and remain largely unknown. The objective of this study is to construct a chemoresistance-related lncRNA-associated competing endogenous RNA (ceRNA) network of pancreatic cancer and identify the key lncRNAs in regulating chemoresistance of the network. Methods Firstly, lncRNA expression profiling of gemcitabine-resistant pancreatic cancer cells was performed to identify lncRNAs related to chemoresistance by microarray analysis. Secondly, with insights into the mechanism of ceRNA, we used a bioinformatics approach to construct a chemoresistance-related lncRNAs-associated ceRNA network. We then identified the topological key lncRNAs in the ceRNA network and demonstrated its function or mechanism in chemoresistance of pancreatic cancer using molecular biological methods. Further studies evaluated its expression to assess its potential association with survival in patients with pancreatic cancer. Results Firstly, we demonstrated that lncRNAs were dysregulated in gemcitabine-resistant pancreatic cancer cells. We then constructed a chemoresistance-related lncRNA-associated ceRNA network and proposed that lncRNA Homo sapiens glutathione S-transferase mu 3, transcript variant 2 and noncoding RNA (GSTM3TV2; NCBI Reference Sequence: NR_024537.1) might act as a key ceRNA to enhance chemoresistance by upregulating L-type amino acid transporter 2 (LAT2) and oxidized low-density lipoprotein receptor 1(OLR1) in pancreatic cancer. Further studies demonstrated that GSTM3TV2, overexpressed in gemcitabine-resistant cells, enhanced the gemcitabine resistance of pancreatic cancer cells in vitro and in vivo. Mechanistically, we identified that GSTM3TV2 upregulated LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance. In addition, we revealed that the expression levels of GSTM3TV2 were significantly increased in pancreatic cancer tissues and were associated with poor prognosis. Conclusion Our results suggest that GSTM3TV2 is a crucial oncogenic regulator involved in chemoresistance and could be a new therapeutic target or prognostic marker in pancreatic cancer.

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