Clinicopathological and prognostic significance of microRNA-107 and its relationship to DICER1 mRNA expression in gastric cancer.
ABSTRACT microRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression. It is known that miRNA-107 (miR-107) promotes cancer invasion and metastasis. However, the relationship between clinicopathological factors and the prognostic significance of miR-107 for gastric cancer patients remains elusive. In this study, we evaluated the prognostic value of miR-107 using tissue samples from gastric cancer patients. Furthermore, the relationship between miR-107 and the mRNA levels of its target gene DICER1 was examined. The expression levels of miR-107 and DICER1 mRNA in tumor tissues and adjacent normal tissues of 161 gastric cancer patients were examined (TNM stage I, 29 patients; stage II, 31 patients; stage III, 51 patients and stage IV, 50 patients). miR-107 levels were measured by Taqman microRNA assays, and DICER1 mRNA levels were measured by the Taqman real-time RT-PCR method. In the analysis by real-time PCR-based miRNA arrays using pooled RNA samples from five gastric cancer patients, expression of miR-107, miR-21, miR-196a, miR-26b, miR-9, miR-142-3p, miR-30b, miR-150, miR-191 and miR-17 was found to be upregulation. The mean expression level of miR-107 was significantly higher in the tumor tissues compared to that of normal tissues. In the comparison of clinicopathological factors, miR-107 expression showed significant association with depth of tumor invasion, lymph node metastasis and stage. In Kaplan-Meier survival curve analysis, overall survival rates (OS) and disease-free survival rates (DFS) of patients with high miR-107 expression were significantly worse than those of patients with low miR-107 expression. In the Cox multivariate analysis, it was shown that miR-107 expression in gastric cancer tissues was an independent prognostic factor for OS and DFS. Significant inverse correlations were demonstrated between miR-107 and DICER1 mRNA. Our results indicate that miR-107 may be useful as an effective biomarker for prediction of a poor prognosis in gastric cancer patients.
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ABSTRACT: Recent evidence shows that altered microRNA-9 (miR-9) expression is implicated in the progression of gastric cancer. However, the exact roles and underlying mechanisms of miR-9 in the proliferation, invasion and metastasis of gastric cancer still remain unknown. In this study, miR-9 was found to be down-regulated and inversely correlated with the expression of cyclin D1 and v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1) in gastric cancer tissues and cell lines. Bioinformatics analysis revealed the putative miR-9 binding sites in the 3'-untranslated regions (3'-UTR) of cyclin D1 and Ets1 mRNA. Ectopic expression or knockdown of miR-9 resulted in responsively altered expression of cyclin D1, Ets1 and their downstream targets phosphorylated retinoblastoma and matrix metalloproteinase 9 in cultured gastric cancer cell lines SGC-7901 and AGS. In the luciferase reporter system, miR-9 directly targeted the 3'-UTR of cyclin D1 and Ets1, and these effects were abolished by mutating the miR-9 binding sites. Over-expression of miR-9 suppressed the proliferation, invasion, and metastasis of SGC-7901 and AGS cells in vitro and in vivo. Restoration of miR-9-mediated down-regulation of cyclin D1 and Ets1 by transient transfection, rescued the cancer cells from decrease in proliferation, migration and invasion. Furthermore, anti-miR-9 inhibitor promoted the proliferation, migration and invasion of gastric cancer cells, while knocking down of cyclin D1 or Ets1 partially phenocopied the effects of miR-9 over-expression. These data indicate that miR-9 suppresses the expression of cyclin D1 and Ets1 via the binding sites in their 3'-UTR, thus inhibiting the proliferation, invasion and metastasis of gastric cancer.PLoS ONE 01/2013; 8(1):e55719. · 3.73 Impact Factor
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ABSTRACT: Introduction: Angiogenesis, for its fundamental role in cancer growth and metastasis, has become an appealing target in cancer therapy. A number of angiogenesis-related microRNAs (miRNAs) are under investigation and they can affect the cancerous phenotype of malignant cells. Areas covered: The authors review the recent advances in angiogenesis-related miRNAs in human colon cancer. They also envisage future developments toward potential miRNA-based applications to cancer treatment. Expert opinion: Angiogenesis-related miRNAs may reasonably be considered as a valuable cancer therapeutic tool. More investigations should be performed to promote therapeutic-clinical research of miRNAs in patients with colon cancer.Expert opinion on biological therapy 11/2012; · 3.22 Impact Factor
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ABSTRACT: Cancers of the oesophagus, gastro-oesophageal junction and stomach (upper gastrointestinal tract cancers; UGICs) pose a major health risk around the world. Collectively, the 5-year survival rate has remained <15%, and therapeutic improvements have been very slow and small. Novel molecules for early diagnosis, prognosis and therapy are, therefore, urgently needed. The role that microRNA (miRNA) molecules have in UGICs are worth pursuing to this end. miRNAs are small noncoding RNA molecules that regulate ∼60% of coding genes in humans and, therefore, are pivotal in mediating and regulating many physiologic processes. miRNAs are deregulated in many disease states, particularly in cancer, making them important targets. Here, we review the growing body of evidence regarding the alterations of miRNAs in UGICs. By suppressing translation and/or promoting degradation of mRNAs, miRNAs can contribute to carcinogenesis and progression of UGICs. In-depth studies of miRNAs in UGICs might yield novel insights and potential novel therapeutic strategies.Nature Reviews Gastroenterology & Hepatology 11/2012; · 10.43 Impact Factor