Inoue T, Iinuma H, Ogawa E, et al. Clinicopathological and prognostic significance of microRNA-107 and its relationship to DICER1 mRNA expression in gastric cancer

Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan.
Oncology Reports (Impact Factor: 2.3). 03/2012; 27(6):1759-64. DOI: 10.3892/or.2012.1709
Source: PubMed

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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    • "For instance, low expression levels of miR-451 and miR-125a-5p are significantly correlated with poor prognosis (Bandres et al., 2009; Nishida et al., 2011). miR-107 expression is an independent prognostic factor for overall survival and disease-free survival (Inoue et al., 2012). However, whether miRNA expression can predict the clinical outcomes of gastric cancer remains to be elucidated. "
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    ABSTRACT: Dysregulated expression of microRNAs (miRNAs) has been shown to be closely associated with tumor development, progression, and carcinogenesis. However, their clinical implications for gastric cancer remain elusive. To investigate the hypothesis that genome-wide alternations of miRNAs differentiate gastric cancer tissues from those matched adjacent non-tumor tissues (ANTTs), miRNA arrays were employed to examine miRNA expression profiles for the 5-pair discovery stage, and the quantitative real-time polymerase chain reaction (qRT- PCR) was applied to validate candidate miRNAs for 48-pair validation stage. Furthermore, the relationship between altered miRNA and clinicopathological features and prognosis of gastric cancer was explored. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be significantly different expressed in tissues from gastric cancer compared to ANTTs (p<0.05). qRT-PCR further confirmed the variation in expression of miR-193b and miR-196a in the validation stage. Down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (p<0.05), while over-expression of miR-196a was significantly associated with poor differentiation (p=0.022). Moreover, binary logistic regression analysis demonstrated that the UICC stage was a significant risk factor for down-expression of miR-193b (adjusted OR=8.69; 95%CI=1.06-56.91; p=0.043). Additionally, Kaplan-Meier survival curves indicated that patients with a high fold-change of down-regulated miR-193b had a significantly shorter survival time (n=19; median survival=29 months) compared to patients with a low fold-change of down-regulated miR-193b (n=29; median survival=54 months) (p=0.001). Overall survival time of patients with a low fold-change of up-regulated miR- 196a (n=27; median survival=52 months) was significantly longer than that of patients with a high fold-change of up-regulated miR-196a (n=21; median survival=46 months) (p=0.003). Hence, miR-193b and miR-196a may be applied as novel and promising prognostic markers in gastric cancer.
    Asian Pacific journal of cancer prevention: APJCP 11/2014; 15(20):8893-900. DOI:10.7314/APJCP.2014.15.20.8893 · 2.51 Impact Factor
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    • "In the Cox multivariate analysis, it was shown that miR-107 expression in GC tissues was an independent prognostic factor for OS and DFS. Their results indicate that miR-107 may be useful as an effective biomarker for prediction of a poor prognosis in GC patients [13]. However, the detailed mechanisms of miR-107 were fewly investigated in GC. "
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    ABSTRACT: Background The biological processes and molecular mechanisms underlying miR-107 remain unclear in gastric cancer(GC). In this study, we aimed to investigate the expression, biological functions and mechanisms of miR-107 in GC.Methods Quantitative real-time RT-PCR was used to test miR-107 expression. MTT and colony formation assays were conducted to explore the potential function of miR-107 in human GC cell line SGC7901. The target gene was determined by bioinformatic algorithms, dual luciferase reporter assay, RT-PCR and Western blot.ResultsExpression of miR-107 was significantly elevated in GC cell line than that in gastric epithelial cell line(p¿=¿0.012). We found that miR-107 inhibitor transfection significantly decreased the proliferation of GC cell line, and clone formation rate of miR-107 inhibitor transfected group was significantly lower than that of control group. Luciferase assays using a reporter carrying a putative miR-107 target site in the 3¿untranslated region (3¿-UTR) of cyclin dependent kinase 8 (CDK8) revealed that miR-107 directly targets CDK8. The expression level of CDK8 mRNA and protein in miR-107 inhibitor transfected GC cell line was significantly decreased compared with control group.Conclusion Our findings indicate that miR-107 is upregulated in GC and affects the proliferation of GC cells, partially through the regulation of CDK8.Virtual SlidesThe virtual slide(s) for this article can be found here:
    Diagnostic Pathology 08/2014; 9(1):164. DOI:10.1186/s13000-014-0164-1 · 2.60 Impact Factor
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    • "Overexpression of miR-191 in 16 different cancer types [breast (female), colon, lung, liver, prostate, pancreas, stomach, ovarian cancer, pituitary adenoma, esophageal squamous carcinoma, oral squamous carcinoma, osteosarcoma, B-ALL, bladder, anaplastic large cell lymphoma, and acute myeloid leukemia (AML)] classifies it largely as an oncogenic miRNA. However, in six other cancer types (severe medulloblastomas, retinoblastoma, thyroid follicular tumor, male breast cancer, CALL, and melanoma) its levels are known to be downregulated (Volinia et al., 2006; Xi et al., 2006; Garzon et al., 2008; Fassan et al., 2009; Ferretti et al., 2009; Fulci et al., 2009; Hui et al., 2009; Kent et al., 2009; Caramuta et al., 2010; Elyakim et al., 2010; Patnaik et al., 2010; Shen et al., 2010; Colamaio et al., 2011; Duan et al., 2011; He et al., 2011; Leite et al., 2011, 2013; Li et al., 2011; Shi et al., 2011; Xu et al., 2011; Inoue et al., 2012; McEvoy et al., 2012; Poliseno et al., 2012; Di Leva et al., 2013; Gombos et al., 2013; Liu et al., 2013a; Nagpal et al., 2013; Zhou et al., 2013; Scheffer et al., 2014). The nature of miR-191 deregulation, its functions and targets reported so far in various cancers are shown in "
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