Identification of Prognostic Biomarkers by Combined mRNA and miRNA Expression Microarray Analysis in Pancreatic Cancer

Liu, Bin; Yang, Hai; Taher, Leila; Denz, Axel; Grützmann, Robert; Pilarsky, Christian; Weber, Georg F.

doi:10.1016/j.tranon.2018.03.003

Cited by 42 publications

(29 citation statements)

References 59 publications

(63 reference statements)

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“…MiRNAs can be used as biological markers for PCs [4,30], and PC is becoming a common malignant disease with an incidence that has continued to rise during the last few years [30,31]. Hence, specific biomarkers for accurate diagnostic tests and potential therapeutic targets for individualized therapy are yet to be fully determined in PDAC.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

et al. 2019

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Pancreatic ductal adenocarcinoma (PDAC) is a class of the commonest malignant carcinomas. The present study aimed to elucidate the potential biomarker and prognostic targets in PDAC. The array data of GSE41368, GSE43795, GSE55643, and GSE41369 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and differentially expressed microRNAs (DEmiRNAs) in PDAC were obtained by using GEO2R, and overlapped DEGs were acquired with Venn Diagrams. Functional enrichment analysis of overlapped DEGs and DEmiRNAs was conducted with Metascape and FunRich, respectively. The protein–protein interaction (PPI) network of overlapped DEGs was constructed by STRING and visualized with Cytoscape. Overall survival (OS) of DEmiRNAs and hub genes were investigated by Kaplan–Meier (KM) plotter (KM plotter). Transcriptional data and correlation analyses among hub genes were verified through GEPIA and Human Protein Atlas (HPA). Additionally, miRNA targets were searched using miRTarBase, then miRNA–DEG regulatory network was visualized with Cytoscape. A total of 32 DEmiRNAs and 150 overlapped DEGs were identified, and Metascape showed that DEGs were significantly enriched in cellular chemical homeostasis and pathways in cancer, while DEmiRNAs were mainly enriched in signal transduction and Glypican pathway. Moreover, seven hub genes with a high degree, namely, V-myc avian myelocytomatosis viral oncogene homolog (MYC), solute carrier family 2 member 1 (SLC2A1), PKM, plasminogen activator, urokinase (PLAU), peroxisome proliferator activated receptor γ (PPARG), MET proto-oncogene, receptor tyrosine kinase (MET), and integrin subunit α 3 (ITGA3), were identified and found to be up-regulated between PDAC and normal tissues. miR-135b, miR-221, miR-21, miR-27a, miR-199b-5p, miR-143, miR-196a, miR-655, miR-455-3p, miR-744 and hub genes predicted poor OS of PDAC. An integrative bioinformatics analysis identified several hub genes that may serve as potential biomarkers or targets for early diagnosis and precision target treatment of PDAC.

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Section: Discussionmentioning

confidence: 99%

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

et al. 2019

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“…miRNAs serve roles in numerous physiological and pathological processes including apoptosis, the cell cycle, cellular growth, proliferation, differentiation, metabolism and aging (6). Accumulating evidence reveals that miRNA dysfunction influences the metastasis, chemo-radioresistance and overall survival time of patients with cancer, including patients with PDAC (7)(8)(9)(10). Previous reports have revealed miRNA involvement in PDAC progression, including roles of miR-216b (11), miR-10a-5p (10), miR-374b-5p (12), miR-1271 (13), miR-7-5p (14), miR-4295 (15) and miR-185 (16).…”

Section: Introductionmentioning

confidence: 99%

miR‑212 regulated by HIF‑1α promotes the progression of pancreatic cancer

2019

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MicroRNA-212 (miR-212) is dysregulated in numerous tissues and cancer types and serves a role in the progression of human cancer. However, the function and mechanism of miR-212 in the development of pancreatic ductal adenocarcinoma (PDAC) remain unknown, particularly in a hypoxic microenvironment. In the present study, miR-212 expression was observed to be significantly upregulated in PDAC tissues compared with normal tissues. Clinical data analysis indicated that miR-212 was positively associated with a large tumor size, Tumor-Node-Metastasis stage, lymph node metastasis and vessel invasion, and influenced the overall survival time. Notably, there was a positive association between the expression of hypoxia-inducible factor-1α (HIF-1α) and miR-212 in vivo and in vitro in hypoxic conditions. Mechanistically, HIF-1α bound directly to a hypoxia response element in the miR-212 promoter region and activated miR-212 expression in PDAC cells. Collectively, these results demonstrated that HIF-1α positively regulated miR-212 expression and resulted in PDAC progression.

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“…In order to identify the miRNA(s), we have mined miRNAs with/for two criteria: (a) miRNA known to be secreted by CD4+ T cells and (b) miRNA known to affect differentiation of CD34+ stem cells in particular through the common myeloid progenitor into the megakaryocytic and erythrocytic lineages.…”

Section: Resultsmentioning

confidence: 99%

HIV‐1 inhibits haematopoiesis via microRNA secreted by virus‐infected CD4+ T cells

Padmanabhan

Dahake

Chowdhary

et al. 2019

European J of Haematology

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Introduction HIV‐1‐infected patients develop haematological disorders such as cytopenias. One possible explanation is the inhibition of haematopoiesis at the level of differentiation of CD34+ haematopoietic progenitor stem cells. Based on our previous studies, we hypothesised that there may be viral encoded, or host cellular factors which participate in the process of inhibition of haematopoiesis. Materials and Methods Virus‐depleted media from infected CD4+ T cells was prepared by filtration and added to CD34+ cell differentiation semisolid medium. We have also used the virus‐depleted media to isolate host/viral factors including miRNA. Isolated miRNAs were screened for their haematopoietic inhibitory function using the miRNA mining approach. Results Addition of virus‐depleted media caused a 40% inhibition of differentiation of CD34+ cells into myeloid and erythroid colony formation. Real‐time RT‐PCR showed miR‐15a and miR‐24 from both pIndie‐C1 and pNL4.3 HIV‐1‐infected cells showed a significant differential expression when compared to control media. Conclusion In this study, we have identified two miRNAs, miR‐15a and miR‐24 secreted from purified HIV‐1‐infected CD4+ T cells that inhibited CD34+ haematopoietic progenitor stem cell differentiation into myeloid and erythroid colonies in vitro.

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Identification of Prognostic Biomarkers by Combined mRNA and miRNA Expression Microarray Analysis in Pancreatic Cancer

Cited by 42 publications

References 59 publications

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

miR‑212 regulated by HIF‑1α promotes the progression of pancreatic cancer

HIV‐1 inhibits haematopoiesis via microRNA secreted by virus‐infected CD4+ T cells

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