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: Background Increasing evidences have documented that microRNAs (miRNAs) act as oncogenes or tumor suppressors in gastric cancer (GC). In this study, we aimed to investigate the expression of miR-133b in a large number of GC samples and elucidate its role in GC carcinogenesis and the detailed mechanism.Methods We used Taqman probe stem-loop real-time PCR to accurately measure the levels of miR-133b in 100 pairs of gastric cancer tissues and the adjacent non-neoplastic tissues. miR-133b mimics were overexpressed in GC cell lines, miR-133b inhibitors were also introduced in GES cells to investigate its role on regulating cell proliferation, cell migration and cell invasion. The target of miR-133b was identified by luciferase reporter assay and western blot. Fascin actin-bundling protein 1 (FSCN1) siRNA was used to achieve the knockdown of FSCN1 in GC cells and to investigate its role on modulating GC cell proliferation and invasion.ResultsmiR-133b was significantly down-regulated in GC cell lines and in GC tissues compared with adjacent normal tissues. Moreover, lower-level of miR-133b was also associated with venous invasion and a more aggressive tumor phenotype. Re-introduction of miR-133b in GC cells can inhibit cell proliferation, cell migration and invasion. In contrary, knockdown of miR-133b in GES cells can promote cell proliferation and invasion. Further investigation indicated that miR-133b targeted FSCN1 in GC cells and knockdown of FSCN1 can also inhibit GC cell growth and invasion.Conclusion Our findings demonstrated that miR-133b was significantly down-regulated in GC tissues and exerted its tumor suppressor role in GC cells. The investigation of the detailed mechanism showed that miR-133b directly targeted FSCN1 which functioned as an oncogenic gene in GC cells. These results suggested that miR-133b can be developed as a new diagnostic marker or therapeutic target for GC.Journal of experimental & clinical cancer research : CR. 11/2014; 33(1):99.
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ABSTRACT: The protein encoded by the TP53 gene is one of the most important suppressors of tumor formation, which is also frequently inactivated in gastrointestinal cancer. MicroRNAs (miRNAs) are small noncoding RNAs that inhibit translation and/or promote degradation of their target messenger RNAs. In recent years, several miRNAs have been identified as mediators and regulators of p53's tumor suppressing functions. p53 induces expression and/or maturation of several miRNAs, which leads to the repression of critical effector proteins. Furthermore, certain miRNAs regulate the expression and activity of p53 through direct repression of p53 or its regulators. Experimental findings indicate that miRNAs are important components of the p53 network. In addition, the frequent genetic and epigenetic alterations of p53-regulated miRNAs in tumors indicate that they play an important role in cancer initiation and/or progression. Therefore, p53-regulated miRNAs may represent attractive diagnostic and/or prognostic biomarkers. Moreover, restoration of p53-induced miRNAs results in suppression of tumor growth and metastasis in mouse models of cancer. Thus, miRNA-based therapeutics may represent a feasible strategy for future cancer treatment. Here we summarize the current published state-of-the-art on the role of the p53-miRNA connection in gastrointestinal cancer.Clinical and experimental gastroenterology. 01/2014; 7:395-413.
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ABSTRACT: Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancer-related death. More than 80% of diagnoses occur at the middle to late stage of the disease, highlighting an urgent need for novel biomarkers detectable at earlier stages. Recently, aberrantly expressed microRNAs (miRNAs) have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis. This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013. Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis, tumor proliferation, distant metastasis and invasion. Furthermore, tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing. As miRNAs in plasma/serum are well protected from RNases, they remain stable under harsh conditions. Thus, potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection. Circulating miRNAs, as well as tissue miRNAs, may allow for the detection of gastric cancer at an early stage, prediction of prognosis, and monitoring of recurrence and/or lymph node metastasis. Taken together, the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer.World journal of gastroenterology : WJG. 09/2014; 20(34):12007-12017.