MicroRNA (miRNA), small non-coding RNA consisted of 19-24 nucleotides, are able to regulate gene expression at the post-transcriptional level. The aberrant expressions of miRNA have been found in various cancers and contribute to carcinogenesis by promoting the expression of proto-oncogenes or by inhibiting the expression of tumor suppressor genes. miRNA are related closely with the oncogenesis, progression, and prognosis of tumors. The discovery of the aberrant expression of miRNA in pancreatic ductal adenocarcinoma (PDA) and its target genes are helpful for the understanding of the pathogenesis of PDA and for the early diagnosis and prediction of this disease. In this paper, we summarize the recent research advances in miRNA expression in PDA and its target genes and discuss the potential role of miRNA in the diagnosis, and treatment of PDA.
Carcinoma, Pancreatic Ductal ; genetics ; Humans ; MicroRNAs ; genetics ; Pancreatic Neoplasms ; genetics

To conduct genetic analysis of pancreatic ductal adenocarcinoma tissues and analyze the correlation between targeted microRNA (miRNA) and pathways in pancreatic ductal adenocarcinoma.
 Methods: We collected 19 samples of peripheral venous blood serum from patients with pancreatic ductal adenocarcinoma in Hainan Provincial Hospital of Chinese Medicine, and also collected 21 blood serum samples as a control group of non-pancreatic ductal adenocarcinoma. We used the bioinformatics analysis of literature GCBI data platform for screening and analyzing the genetics of pancreatic ductal adenocarcinoma samples. Through GCBI data platform of hierarchy clustering analysis and the enrichment of gene function analysis, the relevant miRNA was screened as a research object in patients with pancreatic ductal adenocarcinoma. The miRNA was screened by literature analysis and pancreatic cancer gene analysis. Real-time PCR and Western blotting were carried out to study the relationship between the selected miRNA and TGF-β1 by overexpression and suppression of the gene in pancreatic ductal adenocarcinoma cells.
 Results: MiRNA-21 was screened as a gene associated with pancreatic ductal carcinoma via hierarchy clustering analysis and gene function analysis. MiRNA-21 was highly expressed in the pancreatic ductal carcinoma patients. Expressions of TGF-β1 were inhibired in miRNA-21 overexpressed PANC-1. While the expression of miRNA-21 was inhibited, TGF-β1 expression increased obviously.
 Conclusion: MiRNA-21 is highly expressed in patients with pancreatic ductal adenocarcinoma, can regulate the expression of TGF-β1, which may be a mechanism of miRNA-21 in pancreatic ductal adenocarcinoma.
Carcinoma, Pancreatic Ductal ; genetics ; Humans ; MicroRNAs ; genetics ; Pancreatic Neoplasms ; genetics ; Transforming Growth Factor beta1

Humans ; RNA ; Adenocarcinoma/genetics* ; Pancreatic Neoplasms/genetics* ; Prognosis

Animals ; Carcinoma, Pancreatic Ductal ; genetics ; pathology ; Genes, ras ; genetics ; Humans ; Metaplasia ; MicroRNAs ; genetics ; Mutation ; Pancreatic Ducts ; pathology ; Pancreatic Neoplasms ; genetics ; pathology ; Pancreatitis ; genetics ; Signal Transduction

In the initial genetic studies about pancreatitis in Korea, gene mutations were thought to be rare. However, the recent findings of PRSS1, SPINK1, and CFTR mutations in patients with idiopathic chronic pancreatitis or inherited cases of chronic pancreatitis are much more common than originally predicted. Therefore, it is important to identify underlying genetic background in idiopathic chronic pancreatitis to avoid progression and development of complications. In addition, concentrated and strict follow-up must be given to the patients because of very high risk of pancreatic cancer. However, it is also true that studies about genetics in pancreatitis were not enough to compare with Western studies. Accordingly, further large scale studies are necessary to find other unknown possible genes that could be related to the chronic and hereditary pancreatitis.
Genetics* ; Humans ; Korea ; Pancreatic Neoplasms ; Pancreatitis* ; Pancreatitis, Chronic

Humans ; Pancreatic Neoplasms/genetics* ; Copper ; Apoptosis ; Risk Assessment

Pancreatic cancer is currently the major leading cause of cancer-related deaths in the Western countries with an overall 5-year survival rate of less than 3. The key aim of investigation is to identify the cellular population in which some of the earliest molecular events occur, presumably the ultimate target for carcinogenic insult. Advances in pathological classification and genetics have improved our descriptive understanding of this disease. However, important aspects of pancreatic cancer biology remain poorly understood. Factors associated with the increased risk of pancreatic cancer include smoking, chronic pancreatitis, diabetes, prior gastric surgery, and exposure to radiation or chemicals. A number of syndromes have been identified with the increased incidence of pancreatic cancer, including familial atypical multiple-mole melanoma syndrome, hereditary nonpolyposis colorectal cancer, and hereditary pancreatitis, etc. Recently, there have been growing evidences that stem cell biology could provide new insights into the understanding of cancer biology. Three postulates regarding the relationship between stem and tumor cells have been proposed. First, the similarities in the mechanims that regulate self-renewal of normal stem cells and cancer cells. Second, the possibility that tumor cells might arise from normal stem cells and third, the notion that tumors might contain 'cancer stem cells' - rare cells with indefinite proliferative potential which drive the formation and growth of tumors. New insights for the cancer stem cells and their possible markers in pancreatic cancer have been suggested recently. Further observations of molecular and cellular events in the early stage of pancreatic carcinogenesis may have important implications regarding the cellular lineage responsible for pancreatic ductal metaplasia and neoplasia, and provide further support for the presence of stem cell capabilities within mature pancreatic epithelium.
Carcinoma, Pancreatic Ductal/*etiology/genetics/pathology ; Disease Progression ; Humans ; Mutation ; Neoplasm Proteins/genetics ; Neoplastic Syndromes, Hereditary/genetics ; Oncogenes ; Pancreatic Neoplasms/diagnosis/*etiology/genetics ; Risk Factors ; Tumor Markers, Biological

BACKGROUNDA high mortality rate of pancreatic cancer becomes a bottleneck for further treatment with long-term efficacy. It is urgent to find a new mean to predict the early onset of pancreatic cancer accurately. The authors hypothesized that genetic variants of cationic trypsinogen (PRSS1) gene could affect trypsin expression/function and result in abnormal activation of protease activated receptor-2 (PAR-2), then lead to pancreatic cancer. The aim of this study was to elaborate some novel mutations of PRSS1 gene in the patients with pancreatic cancer.

METHODSTotally 156 patients with pancreatic cancer and 220 unrelated individuals as controls were enrolled in this study. The mutations of PRSS1 gene were analyzed by direct sequencing. K-ras Mutation Detection Kit was used to find the general k-ras gene disorder in the pancreatic cancer tissue. Then the clinical data were collected and analyzed simultaneously.

RESULTSThere were two patients who carried novel mutations which was IVS 3 + 157 G > C of PRSS1 gene in peripheral blood specimens and pancreatic cancer tissue. What's more, it was surprising to find a novel complicated mutation of exon 3 in PRSS1 gene (c.409 A > G and c.416 C > T) in another young patient. The complicated mutation made No. 135 and No. 137 amino acid transfer from Thr to Ala and Thr to Met respectively. No any mutation was found in the normal controls while no mutations of k-ras gene were detected in the three patients.

CONCLUSIONMutations of PRSS1 gene may be an important factor of pancreatic cancer.

Adult ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Mutation ; Pancreatic Neoplasms ; genetics ; Trypsin ; genetics

This study examined the possible role of p120ctn in the pathogenesis and development of pancreatic cancer. PANC-1 cells, a kind of human pancreatic carcinoma cell line, were cultured in this study. p120ctn was immunocytochemically detected in PANC-1 cells. The recombinant lentivirus vector was constructed to knock down the p120ctn expression of PANC-1 cells. Real-time quantitative PCR (RQ-PCR) and Western blotting were used to determine the expression of p120ctn and E-cadherin in PANC-1 cells after p120ctn knockdown. The adhesion, invasion and migration capacity of PANC-1 cells after p120ctn knockdown was detected by cell adhesion, invasion and migration assays. Cell growth was measured by the MTT method. Cell cycle and apoptosis were analyzed by fluorescence-activated cell sorting. The results showed that p120ctn knockdown led to significantly down-regulated E-cadherin and a reduced cell-to-cell adhesion ability in PANC-1 cells. shRNA-mediated knockdown of p120ctn reduced invasion and migration capacity of PANC-1 cells, inhibited cell growth, caused a significant decrease in the percentage of cells in G(1), an increase in S, and promoted apoptosis of PANC-1 cells. It was concluded that p120ctn plays a pivotal role in the proliferation and metastasis of pancreatic carcinoma, suggesting that p120ctn is a novel target for pancreatic carcinoma treatment.
Catenins ; genetics ; Cell Line, Tumor ; Gene Silencing ; Humans ; Pancreatic Neoplasms ; genetics

Carcinoma ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Male ; Pancreatic Neoplasms ; genetics ; Spectral Karyotyping ; methods