scholarly journals PRPF40A as a potential diagnostic and prognostic marker is upregulated in pancreatic cancer tissues and cell lines: an integrated bioinformatics data analysis

2019 ◽  
Vol Volume 12 ◽  
pp. 5037-5051 ◽  
Author(s):  
Zhen Huo ◽  
Shuyu Zhai ◽  
Yuanchi Weng ◽  
Hao Qian ◽  
Xiaomei Tang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Data Analysis ◽  
Prognostic Marker ◽  
Cell Lines ◽  
Cancer Tissues

scholarly journals CircSEC24A upregulates TGFBR2 expression to accelerate pancreatic cancer proliferation and migration via sponging to miR-606

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yankun Chen ◽  
Simiao Xu ◽  
Xinyuan Liu ◽  
Xueyi Jiang ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Cancer Proliferation ◽  
Diagnosis And Prognosis ◽  
Pancreatic Cancer Cells ◽  
Invasive Capacity ◽  
And Migration ◽  
Cancer Tissues

Abstract Background Circular RNA (circRNA), producing by special selective splicing, was widely expressed in the cytoplasm of eukaryotic cells as a newly non-coding RNAs. It played different roles in a variety of diseases including cancer and performed different functions. Nonetheless, reports on the specific function of circRNA in pancreatic cancer (PC) were still rarely so far. In particular, the role of circSEC24A in PC remains unclear. Methods Real-time fluorescent quantitative PCR was used to evaluate the expression level of circSEC24A in pancreatic cancer tissues and cell lines. Furthermore, we used some functional experiments, such as EDU and Transwell assays, to explore the effects of circSEC24A on the proliferation and invasiveness of pancreatic cancer. Finally, the corresponding relationship among circSEC24A, miR-606 and TGFBR2 was explored by dual luciferase reporter and other mechanism studies. Results The expression of circSEC24A in both pancreatic cancer tissues and cell lines was evidently up-regulated. Furthermore, knockdown of circSEC24A significantly inhibited the proliferative, migration and invasive capacity of pancreatic cancer cells, whereas miR-606 inhibitor obviously counteracted these effects. Further study confirmed that circSEC24A alleviated suppression on target TGFBR2 expression by directly sponging miR-606 and then influenced the tumorigenesis of pancreatic cancer. Conclusions These findings indicated that the progression of pancreatic cancer can be driven by circSEC24A influencing miR-606/TGFBR2 axis. Therefore, circSEC24A might be used as a critical biomarker influencing the early diagnosis and prognosis of pancreatic cancer.

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 MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Dan Zhang ◽  
Zhiwei He ◽  
Yiyi Shen ◽  
Jie Wang ◽  
Tao Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Glucose Metabolism ◽  
Cell Lines ◽  
Stress Responses ◽  
Hot Spot ◽  
Luciferase Reporter ◽  
Proliferation And Metastasis ◽  
Cancer Tissues

IntroductionMalignant proliferation and metastasis are some of the causes of high mortality in pancreatic cancer. MicroRNAs have been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. However, the biology function and underlying mechanism of miRNA regulating pancreatic cancer progress is remained uncleared.MethodsRNA-seq analysis the glycolysis associated miRNAs and verified miRNA-489-3p was involving in glycolysis. We used RNA in situ hybridization (ISH) and qRT-PCR to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues and cell lines. Then the function assay of in vivo and in vitro were used to evaluated the role of miR-489-3p in the proliferation, metastasis and glucose metabolism of pancreatic cancer. Furthermore, dual luciferase reporter and rescue experiments were performed to explore the mechanism underlying in the role of miRNA-489-3p.ResultsWe determined that glycolysis associated miRNA miR-489-3p was downregulated in pancreatic cancer tissues and cell lines. The gain and loos of function experiments confirmed that miR-489-3p could inhibit the proliferation, metastasis and glucose metabolism of pancreatic cancer. Further, we found that miR-489-3p could target regulating LDHA and PKM through the luciferase report experiment. Finally, in vivo experiment confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer.ConclusionIn short, this study identified miR-489-3p as a novel therapy target for pancreatic cancer which was involving in the proliferation, metastasis and glycolysis, but its diagnostic value deserves further study.

scholarly journals Increased SPHK1 and HAS2 Expressions Correlate to Poor Prognosis in Pancreatic Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Mengsi Yu ◽  
Kainan Zhang ◽  
Song Wang ◽  
Li Xue ◽  
Zhaoyun Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Receptor Interaction ◽  
Cancer Tissue ◽  
Kaplan Meier ◽  
Short Overall Survival ◽  
Cancer Tissues

Objective. SPHK1 and HAS2 have been reported to play important roles in tumorigenesis and development. However, their expression and prognostic value in pancreatic cancer (PC) remain unclear. This study is aimed at investigating the expression of SPHK1 and HAS2 on the prognosis of pancreatic cancer. Materials and Methods. The expression of SPHK1 and HAS2 in pancreatic cancer tissues was analyzed through TCGA and GTEx databases and validated by qRT-PCR and Western blot in pancreatic cancer cell lines. χ 2 test was used to explore the correlation of the SPHK1 and HAS2 expressions with clinical characteristics. Kaplan-Meier survival analysis and ROC curve were used to evaluate the prognostic and diagnostic roles of SPHK1 and HAS2 in pancreatic cancer. Additionally, Spearman correlation analysis was applied to assess the correlation between the SPHK1 and HAS2 in pancreatic cancer. GO analysis and KEGG analysis were applied to explore the possible signaling pathway that SPHK1 and HAS2 coregulated genes mediated. Results. The expression of SPHK1 and HAS2 was markedly upregulated in pancreatic cancer tissue and cell lines, respectively. Furthermore, there was a significant positive correlation between SPHK1 and HAS2 expressions. ROC curves showed that SPHK1 combine with HAS2 has good diagnostic value in pancreatic cancer patients with 85% sensitivity and 99.4% specificity. Kaplan-Meier analysis showed that increased expression of SPHK1 and HAS2 was significantly associated with short overall survival (OS) of pancreatic cancer patients. GO and KEGG results revealed that SPHK1 and HAS2 mainly involved cell proliferation and invasion mediated by extracellular matrix- (ECM-) receptor interaction, focal adhesion, and PI3K-AKT signaling pathways. Conclusions. Overexpression of SPHK1 and HAS2 could be important markers for the prognosis of pancreatic cancer.

SUV39H1-Mediated DNMT1 is Participated in the Epigenetic Regulation of Smad3 in Cervical Cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Li Zhang ◽  
Sijuan Tian ◽  
Minyi Zhao ◽  
Ting Yang ◽  
Shimin Quan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Epigenetic Regulation ◽  
Promoter Region ◽  
Methylation Status ◽  
Regulation Mechanism ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Immune Factor ◽  
Cancer Tissues

Background: Smad3 is a pivotal intracellular mediator for participating in the activation of multiple immune signal pathway. Objective: The epigenetic regulation mechanism of the positive immune factor Smad3 in cervical cancer remains unknown. Therefore, the epigenetic regulation on Smad3 is investigated in this study. Methods: The methylation status of SMAD3 was detected by Methylation-specific PCR (MS-PCR) and Quantitative Methylation-specific PCR (MS-qPCR) in cervical cancer tissues and cell lines. The underlying molecular mechanisms of SUV39H1-DNMT1-Smad3 regulation was elucidated using cervical cancer cell lines containing siRNA or/and overexpression system. Confirmation of the regulation of DNMT1 by SUV39H1 used Chromatin immunoprecipitation-qPCR (ChIP-qPCR). The statistical methods used for comparing samples between groups were paired t tests and one-way ANOVAs. Results: H3K9me3 protein which regulated by SUV39H1 directly interacts with the DNMT1 promoter region to regulate its expression in cervical cancer cells, resulting in the reduce expression of the downstream target gene DNMT1. In addition, DNMT1 mediates the epigenetic modulation of the SMAD3 gene by directly binding to its promoter region. The depletion of DNMT1 effectively restores the expression of Smad3 in vitro. Moreover, in an in vivo assay, the expression profile of SUV39H1-DNMT1 was found to correlate with Smad3 expression in accordance with the expression at the cellular level. Notably, the promoter region of SMAD3 was hypermethylated in cervical cancer tissues, and this hypermethylation inhibits the subsequent gene expression. Conclusion: These results indicate that SUV39H1-DNMT1 is a crucial Smad3 regulatory axis in cervical cancer. SUV39H1-DNMT1 axis may provide a potential therapeutic target for the treatment of cervical cancer.

scholarly journals Down-regulation LncRNA-SNHG15 contributes to proliferation and invasion of bladder cancer cells

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aldhabi Mokhtar ◽  
Chuize Kong ◽  
Zhe Zhang ◽  
Yan Du
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Tumor Stage ◽  
Rt Pcr ◽  
Down Regulation ◽  
Bladder Cancer Cells ◽  
Cancer Tissues ◽  
Proliferation And Invasion

Abstract Objectives The aim of this study was to investigate the effect of lncRNA-SNHG15 in bladder carcinoma using cell lines experiments and the relationship between clinical characteristics and lncRNA-SNHG15 expression was analyzed. Methods Bladder cancer tissues and near-cancer tissues were collected. The real-time PCR (RT-PCR) was used to detect the expression of lncRNA-SNHG15 in tissues and cell lines. The expression of lncRNA-SNHG15 was downregulated by interference (siRNA), as detected by RT-PCR, that was used to determine the efficiency of the interference. CCK-8 and Transwell assays were used to evaluate the effect of lncRNA-SNHG15 on the proliferation and invasion capability of bladder cancer cells. The t-test was used for Statistical analyses, which were carried out using the Statistical Graph pad 8.0.1.224 software. Result The expression of lncRNA-SNHG15 was up regulated in 5637, UMUC3 and T24 cell lines compared with corresponding normal controls (P < 0.05). Up regulation was positively related to tumor stage (P = 0.015). And tumor size (P = 0.0465). The down-regulation of lncRNA-SNHG15 with siRNA significantly inhibited UMUC3 and T24 cell proliferation and invasion. Conclusion This study showed that lncRNA-SNHG15 is overexpressed in bladder cancer tissues and (5637, UMUC3 T24) cell lines. Up regulation was positively related to tumor stage (P = 0.015), and tumor size (P = 0.0465). Down-regulation of lncRNA-SNHG15 by siRNA significantly inhibited UMUC3 and T24 cell proliferation and invasion, indicating a potential molecular target for future tumor targeted therapy.

scholarly journals Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Wang ◽  
Zhiwei He ◽  
Jian Xu ◽  
Peng Chen ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Loss Of Function ◽  
Mesenchymal Transition

AbstractAn accumulation of evidence indicates that long noncoding RNAs are involved in the tumorigenesis and progression of pancreatic cancer (PC). In this study, we investigated the functions and molecular mechanism of action of LINC00941 in PC. Quantitative PCR was used to examine the expression of LINC00941 and miR-335-5p in PC tissues and cell lines, and to investigate the correlation between LINC00941 expression and clinicopathological features. Plasmid vectors or lentiviruses were used to manipulate the expression of LINC00941, miR-335-5p, and ROCK1 in PC cell lines. Gain or loss-of-function assays and mechanistic assays were employed to verify the roles of LINC00941, miR-335-5p, and ROCK1 in PC cell growth and metastasis, both in vivo and in vitro. LINC00941 and ROCK1 were found to be highly expressed in PC, while miR-335-5p exhibited low expression. High LINC00941 expression was strongly associated with larger tumor size, lymph node metastasis, and poor prognosis. Functional experiments revealed that LINC00941 silencing significantly suppressed PC cell growth, metastasis and epithelial–mesenchymal transition. LINC00941 functioned as a molecular sponge for miR-335-5p, and a competitive endogenous RNA (ceRNA) for ROCK1, promoting ROCK1 upregulation, and LIMK1/Cofilin-1 pathway activation. Our observations lead us to conclude that LINC00941 functions as an oncogene in PC progression, behaving as a ceRNA for miR-335-5p binding. LINC00941 may therefore have potential utility as a diagnostic and treatment target in this disease.

scholarly journals An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

2020 ◽  
Vol 9 (1) ◽  
pp. 192 ◽  
Author(s):  
Alexandre Quilbe ◽  
Olivier Moralès ◽  
Martha Baydoun ◽  
Abhishek Kumar ◽  
Rami Mustapha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Immune System ◽  
Cancer Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Folate Receptor ◽  
Mice Model ◽  
Gene And Protein Expression ◽  
The Impact

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

Gastrin regulates growth of human pancreatic cancer in a tonic and autocrine fashion

1996 ◽  
Vol 270 (5) ◽  
pp. R1078-R1084 ◽  
Author(s):  
J. P. Smith ◽  
A. Shih ◽  
Y. Wu ◽  
P. J. McLaughlin ◽  
I. S. Zagon
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Growth Media ◽  
Human Pancreatic Cancer Cell ◽  
Cell Extracts

The gastrointestinal peptides gastrin and cholecystokinin (CCK) stimulate growth of human pancreatic cancer through a CCK-B/gastrin- like receptor. In the present study we evaluated whether growth of human pancreatic cancer is endogenously regulated by gastrin. Immunohistomical examination of BxPC-3 cells and tumor xenografts revealed specifc gastrin immunoreactivity. Gastrin was detected by radioimmunoassay in pancreatic cancer cell extracts and in pancreatic cancer cell extracts and in the growth media. With use of reverse-transcriptase polymerase chain reaction gastrin gene expression was detected in both cultured BxPC-3 cancer cells and transplanted tumors, as well as seven addition human pancreatic cancer cell lines. Growth of BxPC-3 human pancreatic cancer cell in serum-free medium was inhibited by the addition of the CCK-B/gastrin receptor antagonist L-365,260, and gastrin treatment reversed the inhibitory effect of the antagonist. A selective gastrin antibody (Ab repressed growth of BxPC-3 cells. Gastrin immunoreactivity was detected in fresh human pancreatic cancer specimens but not in normal human pancreatic tissue. These data provide the first evidence that growth of a human pancreatic cancer is tonically stimulated by the autocrine production of gastrin. Evidence for the ubiquity of this system was provided by the detection of gastrin gene expression in multiple human pancreatic cancer cell lines and detection of gastrin in cell lines and fresh pancreatic tumors.

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