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Pancreatic Neoplasms: HELP
Articles by Tao-Yeuan Wang
Based on 12 articles published since 2009
(Why 12 articles?)
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Between 2009 and 2019, Tao Wang wrote the following 12 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article PEG-b-poly (carbonate)-derived nanocarrier platform with pH-responsive properties for pancreatic cancer combination therapy. 2019

Ray, Priyanka / Confeld, Matthew / Borowicz, Pawel / Wang, Tao / Mallik, Sanku / Quadir, Mohiuddin. ·Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, ND, USA. · Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, USA. · Department of Animal Sciences, North Dakota State University, Fargo, ND, USA. · Core Biology Facility, North Dakota State University, Fargo, ND, USA. · Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, USA. Electronic address: sanku.mallik@ndsu.edu. · Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, ND, USA. Electronic address: mohiuddin.quadir@ndsu.edu. ·Colloids Surf B Biointerfaces · Pubmed #30447521.

ABSTRACT: A pH-responsive nanoparticle platform, based on PEG-b-poly (carbonate) block copolymers have been proposed that can respond to low pH as found in many cancer micro- and intracellular environment, including that in pancreatic cancer. The hydrophobic domain, i.e., the poly (carbonate) segment has been substituted with tertiary amine side chains, such as N, N'-dibutylethylenediamine (pK

2 Article Phage-derived protein-mediated targeted chemotherapy of pancreatic cancer. 2018

Wang, Tao / Narayanaswamy, Radhika / Ren, Huilan / Gillespie, James W / Petrenko, Valery A / Torchilin, Vladimir P. ·a Centre for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University , Boston , MA , USA. · b Department of Pathobiology , Auburn University , Auburn , AL , USA. ·J Drug Target · Pubmed #29132246.

ABSTRACT: Pancreatic cancer has been a life-threatening illness associated with high incidence and mortality rates. Paclitaxel (PCT) that causes mitotic arrest in cancer cells disrupting microtubule function is used for pancreatic cancer treatment. Nausea, anorexia and abdominal pain are some of the typical dose-limiting toxicity associated gastrointestinal side effects of the drug. Here, we present the use of polymeric mixed micelles to enable a targeted delivery of PCT and to provide additional advantages such as enhanced drug solubility, bioavailability and minimal dose-limiting toxicity. Also, these micelles self-assemble with pancreatic cancer cells-specific phage proteins P38, L1 and with the hydrophobic drug PCT resolving the issue of complex chemistry efforts normally needed for any conjugation. Our cytotoxicity and binding experiment results in vitro in 2 D and 3 D models suggested that the phage protein-targeted drug-loaded micelles bind and exhibit higher cell killing over the non-targeted ones.

3 Article Inhibition of cancer migration and invasion by knocking down delta-5-desaturase in COX-2 overexpressed cancer cells. 2017

Yang, Xiaoyu / Xu, Yi / Wang, Tao / Shu, Dan / Guo, Peixuan / Miskimins, Keith / Qian, Steven Y. ·Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA. · Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, and College of Medicine, Ohio State University, Columbus, OH 43210, USA. · Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA. · Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA. Electronic address: steven.qian@ndsu.edu. ·Redox Biol · Pubmed #28157665.

ABSTRACT: We recently reported that knockdown of delta-5-desaturase (a key enzyme that converts dihomo-γ-linolenic acid, DGLA, to the downstream ω-6 arachidonic acid) promotes formation of an anti-cancer byproduct 8-hydroxyoctanoic acid from cyclooxygenase (COX)-catalyzed DGLA peroxidation. 8-hydroxyoctanoic acid can exert its growth inhibitory effect on cancer cells (e.g. colon and pancreatic cancer) by serving as a histone deacetylase inhibitor. Since histone deacetylase inhibitors have been well-known to suppress cancer cell migration and invasion, we thus tested whether knockdown of delta-5-desaturase and DGLA treatment could also be used to inhibit cancer migration and invasion of colon cancer and pancreatic cancer cells. Wound healing assay, transwell assay and western blot were used to assess cell migration and invasion as well as the associated molecular mechanisms. Formation of threshold level of 8-hydroxyoctanoic acid was quantified from COX-catalyzed DGLA peroxidation in the cancer cells that overexpress COX-2 and their delta-5-desaturases were knocked down by shRNA transfection. Our results showed that knockdown of delta-5-desaturase along with DGLA supplement not only significantly inhibited cell migration, but also improved the efficacies of 5-flurouracil and gemcitabine, two frontline chemotherapy drugs currently used in the treatment of colon and pancreatic cancer, respectively. The molecular mechanism behind these observations is that 8-hydroxyoctanoic acid inhibits histone deacetylase, resulting in downregulation of cancer metastasis promotors, e.g., MMP-2 and MMP-9 as well as upregulation of cancer metastasis suppressor, e.g. E-cadherin. For the first time, we demonstrated that we could take the advantage of the common phenomenon of COX-2 overexpression in cancers to inhibit cancer cell migration and invasion. With the shifting paradigm of COX-2 cancer biology, our research outcome may provide us a novel cancer treatment strategy.

4 Article Senescent Carcinoma-Associated Fibroblasts Upregulate IL8 to Enhance Prometastatic Phenotypes. 2017

Wang, Tao / Notta, Faiyaz / Navab, Roya / Joseph, Joella / Ibrahimov, Emin / Xu, Jing / Zhu, Chang-Qi / Borgida, Ayelet / Gallinger, Steven / Tsao, Ming-Sound. ·Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. · Department of Pathology, University Health Network, Toronto, Canada. · Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. · Ontario Institute for Cancer Research, Toronto, Canada. · Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Canada. · Department of General Surgery, University Health Network, Toronto, Canada. · Department of Surgery, University of Toronto, Toronto, Canada. · Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. ming.tsao@uhn.ca. ·Mol Cancer Res · Pubmed #27678171.

ABSTRACT: Carcinoma-associated fibroblasts (CAF) represent a significant component of pancreatic cancer stroma and are biologically implicated in tumor progression. However, evidence of both cancer-promoting and -restraining properties amongst CAFs suggests the possibility of multiple phenotypic subtypes. Here, it is demonstrated that senescent CAFs promote pancreatic cancer invasion and metastasis compared with nonsenescent control CAFs using in vitro Transwell invasion models and in vivo xenograft mouse models. Screening by gene expression microarray and cytokine ELISA assays revealed IL8 to be upregulated in senescent CAFs. Experimental modulation through IL8 overexpression or receptor inhibition implicates the IL8 pathway as a mediator of the proinvasive effects of senescent CAFs. In a cohort of human pancreatic cancer cases, more abundant stromal senescence as indicated by p16 immunohistochemistry correlated with decreased survival in patients with early-stage disease. These data support senescent fibroblasts as a pathologically and clinically relevant feature of pancreatic cancer. The inhibition of senescent stroma-cancer signaling pathways has the potential to restrain pancreatic cancer progression. IMPLICATIONS: Findings show that senescent cancer-associated fibroblasts secret excess IL8 to promote pancreatic cancer invasion and metastasis; thus, senescent CAFs represent a phenotypic subtype, challenging conventional assumptions that CAFs are a homogeneous population. Mol Cancer Res; 15(1); 3-14. ©2016 AACR.

5 Article Targeting Epithelial-Mesenchymal Transition for Identification of Inhibitors for Pancreatic Cancer Cell Invasion and Tumor Spheres Formation. 2016

Polireddy, Kishore / Dong, Ruochen / McDonald, Peter R / Wang, Tao / Luke, Brendan / Chen, Ping / Broward, Melinda / Roy, Anuradha / Chen, Qi. ·Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, Kansas, United States of America. · High-Throughput Screening Core Facility, Structural Biology Center, University of Kansas, Lawrence, Kansas, United States of America. ·PLoS One · Pubmed #27764163.

ABSTRACT: BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition. METHODS: An immunofluorescent assay was established and optimized for HTS to identify compounds that enhance E-cadherin expression, as a hallmark of inhibition of EMT. Four chemical libraries containing 41,472 compounds were screened in PANC-1 pancreatic cancer cell line. Positive hits were validated for EMT and CSC inhibition in vitro using sphere formation assay, western blotting, immune fluorescence, and scratch assay. RESULTS: Initial hits were refined to 73 compounds with a secondary screening, among which 17 exhibited concentration dependent induction of E-cadherin expression. Six compounds were selected for further study which belonged to 2 different chemical structural clusters. A novel compound 1-(benzylsulfonyl) indoline (BSI, Compound #38) significantly inhibited pancreatic cancer cell migration and invasion. BSI inhibited histone deacetylase, increased histone 4 acetylation preferably, resulting in E-cadherin up-regulation. BSI effectively inhibited tumor spheres formation. Six more analogues of BSI were tested for anti-migration and anti-CSC activities. CONCLUSION: This study demonstrated a feasible approach for discovery of agents targeting EMT and CSCs using HTS, and identified a class of novel chemicals that could be developed as anti-EMT and anti-CSC drug leads.

6 Article A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns. 2016

Notta, Faiyaz / Chan-Seng-Yue, Michelle / Lemire, Mathieu / Li, Yilong / Wilson, Gavin W / Connor, Ashton A / Denroche, Robert E / Liang, Sheng-Ben / Brown, Andrew M K / Kim, Jaeseung C / Wang, Tao / Simpson, Jared T / Beck, Timothy / Borgida, Ayelet / Buchner, Nicholas / Chadwick, Dianne / Hafezi-Bakhtiari, Sara / Dick, John E / Heisler, Lawrence / Hollingsworth, Michael A / Ibrahimov, Emin / Jang, Gun Ho / Johns, Jeremy / Jorgensen, Lars G T / Law, Calvin / Ludkovski, Olga / Lungu, Ilinca / Ng, Karen / Pasternack, Danielle / Petersen, Gloria M / Shlush, Liran I / Timms, Lee / Tsao, Ming-Sound / Wilson, Julie M / Yung, Christina K / Zogopoulos, George / Bartlett, John M S / Alexandrov, Ludmil B / Real, Francisco X / Cleary, Sean P / Roehrl, Michael H / McPherson, John D / Stein, Lincoln D / Hudson, Thomas J / Campbell, Peter J / Gallinger, Steven. ·Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada. · Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. · UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, Ontario M5G 2C4, Canada. · Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada. · Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. · Department of Computer Science, University of Toronto, Toronto, Ontario M5S 3G4, Canada. · Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, Nebraska 68198, USA. · Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. · Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario M5G 2M9, Canada. · Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, Ontario M4N 3M5, Canada. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA. · Research Institute of the McGill University Health Centre, Montreal, Québec, Canada, H3H 2L9. · Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico, USA, 87545. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. · Department of Surgery, University Health Network, Toronto, Ontario M5G 2C4, Canada. · Department of Haematology, University of Cambridge, Cambridge CB2 0XY, UK. ·Nature · Pubmed #27732578.

ABSTRACT: Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours.

7 Article Negative correlation of ITCH E3 ubiquitin ligase and miRNA-106b dictates metastatic progression in pancreatic cancer. 2016

Luo, Zhu-Lin / Luo, Hui-Jun / Fang, Chen / Cheng, Long / Huang, Zhu / Dai, Ruiwu / Li, Kun / Tian, Fu-Zhou / Wang, Tao / Tang, Li-Jun. ·Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China. · Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA. · Chengdu Military Institute for Drug and Instrument Control, Chengdu, Sichuan 610020, P. R. China. · Medical Central Laboratory, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China. ·Oncotarget · Pubmed #26621835.

ABSTRACT: Pancreatic cancer is one of the major malignancies and cause for mortality across the world, with recurrence and metastatic progression remaining the single largest cause of pancreatic cancer mortality. Hence it is imperative to develop novel biomarkers of pancreatic cancer prognosis. The E3 ubiquitin ligase ITCH has been previously reported to inhibit the tumor suppressive Hippo signaling by suppressing LATS1/2 in breast cancer and chronic lymphocytic leukemia. However, the role of ITCH in pancreatic cancer progression has not been described. Here we report that ITCH transcript and protein expression mimic metastatic trait in pancreatic cancer patients and cell lines. Loss-of-function studies of ITCH showed that the gene product is responsible for inducing metastasis in vivo. We furthermore show that hsa-miR-106b, which itself is down regulated in metastatic pancreatic cancer, directly interacts and inhibit ITCH expression. ITCH and hsa-miR-106b are thus potential biomarkers for pancreatic cancer prognosis.

8 Article Transcriptomic analysis of pancreatic cancer cells in response to metformin and aspirin: an implication of synergy. 2015

Yue, Wen / Wang, Tao / Zachariah, Emmanuel / Lin, Yong / Yang, Chung S / Xu, Qing / DiPaola, Robert S / Tan, Xiang-Lin. ·Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901. · Department of Epidemiology &Population Health, Albert Einstein College of Medicine, Bronx, NY 10461. · Department of Biostatistics, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, NJ 08854. · Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854. · Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072. · Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, NJ 08854. ·Sci Rep · Pubmed #26294325.

ABSTRACT: Metformin and aspirin have been studied extensively as cancer preventative and therapeutic agents. However, the underlying molecular mechanisms for the inhibitory effects of pancreatic cancer development remain undefined. To gain further insight into their biological function in pancreatic cancer, we conducted a transcriptomic analysis using RNA sequencing to assess the differential gene expression induced by metformin (5 mM) and aspirin (2 mM), alone or in combination, after treatment of PANC-1 cells for 48 hours. Compared to an untreated control, metformin down-regulated 58 genes and up-regulated 91 genes, aspirin down-regulated 12 genes only, while metformin plus aspirin down-regulated 656 genes and up-regulated 449 genes (fold-change > 2, P < 10(-5)). Of the top 10 genes (fold-change > 10, P < 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated ≥ 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated ≥ 10-fold. Ingenuity Pathway Analysis (IPA) revealed that the pathways, "cholesterol biosynthesis", "cell cycle: G1/S checkpoint regulation", and "axonal guidance signaling" were the most statistically significant pathways modulated by metformin plus aspirin. Although the results need further functional validation, these data provide the first evidence for the synergistic action between metformin and aspirin in modulating the transcriptional profile of pancreatic cancer cells.

9 Article A comparison of the clinical features and prognosis of pancreatic head cancer with that of other periampullary cancers. 2013

Liang, Ye Min / Wang, Tao / Sun, Qi Long / Cheng, Yu Feng. · ·Hepatogastroenterology · Pubmed #23165191.

ABSTRACT: BACKGROUND/AIMS: Our purpose was to compare the clinical features and prognosis of pancreatic head cancer with that of other periampullary cancers. METHODOLOGY: The medical records of 82 patients (mean age of 61.67±10.52 years) with ductal adenocarcinoma of the head of pancreas and 73 patients (mean age of 60.52±11.72 years) with other periampullary adenocarcinomas, all of whom had received radical surgery, were retrospectively analyzed. RESULTS: There were no significant differences in age and gender between the groups (both, p>0.05). However, there were significant differences in lymph node metastasis, TNM stage, clear surgical margins, tumor size, and neural invasion between the 2 groups (all p<0.05). Patients with pancreatic head adenocarcinoma had significantly higher red blood cell (RBC) count and hemoglobin (Hb), albumin and pre-albumin levels, and higher platelet and white blood cell (WBC) counts than the patients with other periampullary adenocarcinomas (all p<0.05). No differences in carcinoembryonic antigen (CEA) or CA19-9 were noted between the groups. The 1-year survival rates were not different between the groups (p=0.299). CONCLUSIONS: Pancreatic head carcinoma has different clinical manifestations and biological features than other periampullary cancers.

10 Article Transactivation of the human NME5 gene by Sp1 in pancreatic cancer cells. 2012

Li, Fu / Jiang, Zhenzhou / Wang, Ke / Guo, Jingjing / Hu, Gang / Sun, Lixin / Wang, Tao / Tang, Xuzhen / He, Ling / Yao, Jincheng / Wen, Danyi / Qin, Xiaoran / Zhang, Luyong. ·Jiangsu Center of Drug Screening, China Pharmaceutical University, No. 24 Tongjia Xiang, Nanjing, Jiangsu Province, China. ·Gene · Pubmed #22564704.

ABSTRACT: Non-metastatic cells 5 (NME5), a recently found gene belonging to the NDPK-like molecules gene family, is highly expressed in testis and some types of human cancer. Current studies have revealed diverse potential functions of NME5 and we have reported that NME5 is associated with innate resistance to gemcitabine in human pancreatic cancer cells in previous study. However, the mechanism underlying the transcriptional regulation of NME5 has not been elucidated yet. In this study, we analyzed the 5'-flanking region of the human NME5 gene and revealed its transcription start site (TSS) at -35 bp relative to its translation start codon ATG. Using 5' unidirectional deletion analysis, we demonstrated that the proximal promoter of NME5 is located within -1051 bp to +35 bp. Two functional GC-boxes (-300 bp and -323 bp) were identified within the promoter region. Mutation of either GC-box led to significant reduction in NME5 promoter activity, whereas overexpression of Sp1 activated NME5 promoter activity in MIA PaCa-2 and 293T cells. In silico analysis predicted that transcription factor Sp1 binds to both GC-boxes, which were confirmed by EMSA and ChIP. In addition, we found that compared with MIA PaCa-2, Sp1 was highly expressed in PAXC002, a well characterized human pancreatic cancer cell line with innate gemcitabine resistance where NME5 was reported to be highly expressed, indicating that Sp1 induces NEM5 expression in PAXC002 cells. In conclusion, our study characterized for the first time the human NME5 promoter which is controlled by Sp1 transcription factor in pancreatic cancer.

11 Article Pancreatic head well-differentiated endocrine tumor. 2011

Hu, Kuang-Chun / Chang, Wen-Hsiung / Chu, Cheng-Hsin / Wang, Tsang-En / Wang, Tao-Yeuan / Lee, Jie-Jen / Shih, Shou-Chuan. ·Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Taipei, Taiwan. ·Am J Surg · Pubmed #21367361.

ABSTRACT: The authors report a case of a small pancreatic head well-differentiated endocrine tumor. A 44-year-old woman was revealed to have a large cystic tumor in the pancreatic head area. Resection revealed a well-differentiated endocrine tumor 7 mm in diameter confined to the pancreatic head and obstructing the proximal portion of the pancreatic duct, resulting in cystic dilatation of the duct, mimicking a cystic tumor of the pancreatic head.

12 Retraction miR-663 attenuates tumor growth and invasiveness by targeting eEF1A2 in pancreatic cancer. 2015

Zang, Wenqiao / Wang, Yuanyuan / Wang, Tao / Du, Yuwen / Chen, Xiaonan / Li, Min / Zhao, Guoqiang. ·College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan Province, China. zangwenqiao@sina.com. · College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan Province, China. 50998719@qq.com. · Department of Hemato-tumor, The First Affiliated Hospital of Henan University of TCM, Zhengzhou, 450000, China. wang0371@126.com. · College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan Province, China. yuwen0107@126.com. · College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan Province, China. chenxiaonan09@126.com. · College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan Province, China. limin75@163.com. · College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan Province, China. zhaogq@zzu.edu.cn. ·Mol Cancer · Pubmed #25744894.

ABSTRACT: BACKGROUND: miR-663 is associated with many important biologic processes, such as the evolution, development, viral infection, inflammatory response, and carcinogenesis among vertebrates. However, the molecular function and mechanism of miR-663 in pancreatic cancer growth and invasion is still unclear. METHODS: Western blot and real-time PCR were used to study the expression level of eEF1A2 protein and miR-663 in pancreatic cancer tissues and cell lines. The Pearson χ (2) test was used to determine the correlation between miR-663 expression and clinicopathologic features of patients. Patients' survival was analyzed using the Kaplan-Meier method, using the log-rank test for comparison. The biological function of miR-663 was examined by measuring cell growth, cell invasion and apoptosis analysis in vitro and in vivo. miR-663 target gene and signaling pathway was identified by luciferase activity assay and western blot. RESULTS: We found that, in pancreatic cancer, eEF1A2 was significantly upregulated but miR-663 was significantly downregulated. Further results showed that the expression level of eEF1A2 and miR-663 was strongly associated with TNM stage and node metastasis status of the patients. miR-663 and eEF1A2 were inversely correlated with each other, and the changes in the expression levels of each can also predict the survival of patients with pancreatic cancer. We identified miR-663 as a tumor attenuate molecular that attenuated the proliferation and invasion of pancreatic cancer cells both in vitro and in vivo. Finally, we confirmed that the expression of eEF1A2 can partially restore the pro-apoptotic and anti-invasion functions of miR-663. CONCLUSIONS: miR-663 attenuated the proliferation and invasion of pancreatic cells both in vitro and in vivo by directly targeting eEF1A2. miR-663 and eEF1A2 might be potential targets for the treatment of pancreatic cancer in the future.