MiR-21, miR-34a, miR-198 and miR-217 as diagnostic and prognostic biomarkers for chronic pancreatitis and pancreatic ductal adenocarcinoma

Vychytilova-Faltejskova, Petra; Kiss, Igor; Klusova, Sona; Hlavsa, Jan; Procházka, Vladimír; Kala, Zdeněk; Mazanec, Jan; Hausnerová, Jitka; Křen, Leoš; Hermanová, Markéta; Lenz, Jiří; Karásek, Petr; Vyzula, Rostislav; Slabý, Ondřej

doi:10.1186/s13000-015-0272-6

Cited by 62 publications

(54 citation statements)

References 25 publications

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“…Hence, emerging studies have discovered that the differential expression of miRNA, such as miR-21, miR-99a, and miR-34a, could predict the prognosis of PaCa patients [16][17][18]. In pancreatic tumor tissue, aberrant expression of miRNAs, such as miR-21, miR-221, miR-34a, and miR-217, were reported, which suggested that these molecular regulators had the potential to serve as biomarkers [17,[19][20][21]. Meta-analyses were conducted to evaluate the diagnostic value of miRNAs, and they showed moderate predictive values for PaCa diagnosis [22,23].…”

Section: Introductionmentioning

confidence: 99%

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Zhang

Pan

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies. Methods: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools. Results: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59–0.93], and AUC: 0.84 [95% CI 0.73–0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region. Conclusion: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients.

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Section: Introductionmentioning

confidence: 99%

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Zhang

Pan

et al. 2018

Cell Physiol Biochem

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“…miRNAs have been implicated in a variety of biological processes, including embryonic development, cell differentiation and diseases including human cancer (3). miR-198 has been reported to be deregulated in several human cancers, including colorectal (4), lung (5), pancreatic (6,7), hepato cellular (8,9), prostate (10) and esophageal cancer (11). However, the involvement and effects of miR-198 on breast cancer progression and the underlying mechanism remain unknown.…”

Section: Introductionmentioning

confidence: 99%

miR-198 functions as a tumor suppressor in breast cancer by targeting CUB domain-containing protein 1

Tang

Jiang

et al. 2017

Oncology Letters

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Abstract. The molecular mechanisms underlying the dysregulation of microRNAs (miRs) have been previously documented in breast cancer. miR-198 has been reported to be deregulated in several human cancers. However, the detailed effects of miR-198 on breast cancer progression remain unclear. Using quantitative polymerase chain reaction analysis, we demonstrated in the present study that miR-198 was downregulated in breast cancer tissues and cell lines, and that downregulation of miR-198 was significantly correlated with lymph node metastasis. Functional studies revealed that miR-198 inhibited cell proliferation and migration and promoted cell adhesion in aggressive breast cancer cells in vitro. In addition, we observed that CUB domain-containing protein 1 (CDCP1) was a direct target of miR-198, and that knockdown of CDCP1 inhibited cell proliferation and migration, and promoted cell adhesion, which was similar to the effects of overexpression of miR-198. Taken together, we provide evidence to characterize the role of miR-198/CDCP1 interaction in breast cancer, which may be useful in breast cancer therapy.

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“…The low expression level of miR-217 was notably correlated with tumor differentiation and shorter overall survival for patients with colorectal cancer (24). Additionally, miR-217 was found to be downregulated in lung (25), hepatocellular (26) and clear cell renal cell carcinoma (27) and pancreatic ductal adenocarcinoma (28). However, in breast cancer, miR-217 was upregulated in tumor tissues in comparison with normal breast tissues.…”

Section: Discussionmentioning

confidence: 84%

MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS

Xiao

Deng

et al. 2017

Oncology Letters

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Abstract. Acute myeloid leukemia (AML) is a heterogeneous malignant disorder derived from the myeloid hematopoietic cells that accounts for ~80% of all adult acute leukemia. Numerous studies have shown that drug resistance not only exists against conventional chemotherapeutic drugs, but also limits the efficacy of new biological agents. Therefore, it is important to identify the mechanisms behind chemoresistance and seek therapeutic strategies to enhance efficacy in AML chemotherapy. MicroRNA (miR)-217 has been recognized as a tumor suppressor that is downregulated in various types of cancer, however the mechanisms behind the expression and function of miR-217 in AML have not yet been recognized. The expression of miR-217 was determined by quantitative polymerase chain reaction (qPCR). Following transfection with miR-217 mimics, an MTT assay, chemosensitivity assay, cell apoptosis assay and western blot analysis were performed in AML cell lines. Functional assays were also performed to explore the effects of endogenous Kirsten rat sarcoma viral oncogene homolog (KRAS) in AML. The results revealed that miR-217 was downregulated in patients with AML. Overexpression of miR-217 inhibited cellular proliferation and enhanced cell chemosensitivity to doxorubicin by the cell apoptosis pathway in AML cells. A dual-luciferase reporter assay demonstrated that KRAS was a direct target gene of miR-217 in vitro. qPCR and western blot analysis revealed that miR-217 negatively regulated KRAS protein expression, but had no impact on KRAS mRNA expression. Knockdown of KRAS expression markedly suppressed AML cellular proliferation, and enhanced cell chemosensitivity to doxorubicin via the cell apoptosis pathway. These findings indicate that miR-217 functions as a tumor suppressor in AML by directly targeting KRAS. Therefore, miR-217-based therapeutic strategies may provide a novel strategy for the enhancement of efficacy in the treatment of AML.

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MiR-21, miR-34a, miR-198 and miR-217 as diagnostic and prognostic biomarkers for chronic pancreatitis and pancreatic ductal adenocarcinoma

Cited by 62 publications

References 25 publications

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

miR-198 functions as a tumor suppressor in breast cancer by targeting CUB domain-containing protein 1

MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS

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