Diagnostic and biological significance of microRNA-192 in pancreatic ductal adenocarcinoma

Zhao, Chenyan; Zhang, Jing; Zhang, Shu‐Hui; Yu, Danghui; Chen, Ying; Liu, Qinghua; Shi, Min; Chen, Ni; Zhu, Min

doi:10.3892/or.2013.2420

Cited by 83 publications

(77 citation statements)

References 32 publications

(44 reference statements)

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“…miR-192 expression was found to be downregulated significantly enough to serve as an accurate diagnostic marker of PDAC and CP, in contrast to a recent report (24). Its abnormal expression in PDAC and CP was mediated by DNA methylation at the same genomic locus within the promoter region, which showed a significant inverse correlation with the miR-192 expression in individual patients of the cohort.…”

Section: Discussioncontrasting

confidence: 88%

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

et al. 2016

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Pancreatic ductal adenocarcinoma (PDAC) is characterized by very early metastasis, suggesting the hypothesis that metastasisassociated changes may occur prior to actual tumor formation. In this study, we identified miR-192 as an epigenetically regulated suppressor gene with predictive value in this disease. miR-192 was downregulated by promoter methylation in both PDAC and chronic pancreatitis, the latter of which is a major risk factor for the development of PDAC. Functional studies in vitro and in vivo in mouse models of PDAC showed that overexpression of miR-192 was sufficient to reduce cell proliferation and invasion. Mechanistic analyses correlated changes in miR-192 promoter methylation and expression with epithelial-mesenchymal transition. Cell proliferation and invasion were linked to altered expression of the miR-192 target gene SERPINE1 that is encoding the protein plasminogen activator inhibitor-1 (PAI-1), an established regulator of these properties in PDAC cells. Notably, our data suggested that invasive capacity was altered even before neoplastic transformation occurred, as triggered by miR-192 downregulation. Overall, our results highlighted a role for miR-192 in explaining the early metastatic behavior of PDAC and suggested its relevance as a target to develop for early diagnostics and therapy.

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Section: Discussioncontrasting

confidence: 88%

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

et al. 2016

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“…The abnormal expression of miRNAs in PDAC was previously reported (24)(25)(26); however, few studies have investigated the role of specific miRNAs in carcinogenesis and progression of PDAC. The present study has presented the first data characterizing the expression, biological functions and molecular mechanisms underlying miR-216b in PDAC.…”

Section: Discussionmentioning

confidence: 95%

MicroRNA‑216b reduces growth, migration and invasion of pancreatic ductal adenocarcinoma cells by directly targeting ρ‑associated coiled‑coil containing protein kinase 1

et al. 2018

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Abstract. Developments in cancer therapy have greatly improved the survival time for patients with pancreatic ductal adenocarcinoma (PDAC); however, the prognosis of patients with PDAC remains poor. Understanding the expression patterns and functions of microRNAs may provide strategies for the diagnosis and treatment of patients with PDAC. The present study aimed to explore the expression and functions of microRNA-216b (miR-216b) in PDAC. The expression of miR-216b in PDAC tissues and cell lines was quantified with reverse transcription-quantitative polymerase chain reaction. An miR-216b mimic was introduced into PDAC cells to induce the effects of miR-21b overexpression. The effects of miR-216b overexpression on growth, migration and invasion of PDAC cells were evaluated by cell proliferation assay, migration and invasion assays, respectively. The molecular mechanism underlying the suppressive effects of miR-216b on PDAC was also examined; a direct target gene of miR-216b, ρ-associated coiled-coil containing protein kinase 1 (ROCK1), was downregulated by ROCK1 short interfering RNA to investigate the effects on growth, migration and invasion of PDAC cells. The present study revealed that miR-216b was significantly downregulated in PDAC tissues and cell lines. Overexpression of miR-216b inhibited growth, migration and invasion of PDAC cells in vitro. ROCK1 was identified as a direct target gene of miR-216b in pancreatic cancer and the downregulation of ROCK1 resembled the effects of miR-216b overexpression in PDAC cells. Taken together, miR-216b acted as a tumor suppressor in PDAC and may represent a novel therapeutic target in PDAC.

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“…Previous studies found that miR-192 is significantly increased in many types of cancer (39)(40)(41), but decreased in many others (42,43). Studies have also shown that p53-mediated upregulation of miR-192 prevents EMT in hepatocellular carcinoma through repression of the transcription factor ZEB2 (44).…”

Section: Discussionmentioning

confidence: 98%

Plasma miR-122 and miR-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer

Chen

Zhang

et al. 2014

Oncology Reports

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Abstract. The aim of the present study was to ascertain whether plasma levels of specific microRNAs (miRNAs) are associated with distant metastasis (DM) in gastric cancer (GC). miRNA profiling was performed on 12 pairs of samples of gastric cancer with distant metastasis (GC/DM) and gastric cancer with no distant metastasis (GC/NDM); 14 differentially expressed miRNAs were identified for further inspection. Validation of these 14 miRNAs using quantitative reverse transcription PCR (qRT-PCR) on an independent validation set identified 2 differentially expressed miRNAs (miR-122 and miR-192). Further validation of these two candidate miRNAs was conducted in a disease control set, a self-paired plasma set and finally in gastric cell lines in vitro. The results revealed that when compared with GC/NDM and healthy controls (HCs), plasma levels of miR-122 were significantly lower and plasma levels of miR-192 were significantly higher in GC/DM samples (both P<0.01). The plasma miR-122 level was again lower and the plasma miR-192-level was again higher in patients with GC/DM than in patients with benign gastric ulcer (BGC) and chronic gastritis (CG) (P<0.01). Compared to the level in patients with pre-distant metastases, miR-122 was significantly decreased while miR-192 was markedly elevated in patients with post-distant metastases (P<0.01). In CTC105 and CTC141 cells, miR-122 levels were moderately lower and miR-192 levels were markedly higher when compared to the levels in the GES-1 cells. ROC analyses showed that the AUC for plasma miR-122 was 0.808 (95% CI, 0.712-0.905; P<0.01), and the AUC for plasma miR-192 was 0.732 (95% CI, 0.623-0.841; P<0.01) for distinguishing GC/ DM from GC/NDM. High expression of miR-122 in plasma independently contributed to a more favorable prognosis for GC (hazard ratio, 0.262; 95% CI, 0.164-0.816; P= 0.038; Cox regression analysis), whereas the miR-192 level was not associated with the overall survival time. Our results demonstrated that assessment of decreased circulating miR-122 and elevated circulating miR-192 levels has the potential to improve early detection of DM in GC. Higher plasma levels of miR-122 in GC may indicate a favorable prognosis.

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Diagnostic and biological significance of microRNA-192 in pancreatic ductal adenocarcinoma

Cited by 83 publications

References 32 publications

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

MicroRNA‑216b reduces growth, migration and invasion of pancreatic ductal adenocarcinoma cells by directly targeting ρ‑associated coiled‑coil containing protein kinase 1

Plasma miR-122 and miR-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer

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