Expression Levels Of miR-107 Research Articles

Aberrant plasma levels of circulatingmiR-16, miR-107, miR-130aandmiR-146aare associated with lymph node metastasis and receptor status of breast cancer patients

Within the multicenter SUCCESS trial, we investigated the association of plasma microRNAs with different subtypes of invasive breast cancer.Six miRs (miR-16, miR-27a, miR-107, miR-130a, miR-132 and miR-146a) were selected from microarray profiling and further validated in plasma of 111 breast cancer patients before and after chemotherapy and 46 healthy women by quantitative real-time PCR.Plasma levels of miR-16 (p = 0.0001), miR-27a (p = 0.039) and miR-132 (p = 0.020) were higher in breast cancer patients before chemotherapy than healthy women. With the exception of miR-16, the increased levels of miR-27a (p = 0.035) and miR-132 (p = 0.025) decreased after chemotherapy to those observed in healthy women. Levels of miR-16 (p = 0.019), miR-107 (p = 0.036), miR-130a (p = 0.027) and miR-146a (p = 0.047) were different between lymph node -positive and -negative patients, while the levels of miR-130a (p = 0.001) and miR-146a (p = 0.025) also differed between HER2-positive and -negative status. Estrogen-receptor negative tumors displayed higher concentrations of circulating miR-107 than their counterparts (p = 0.035). However, overexpression of miR-107 in MCF-7 cells did not downregulate estrogen receptor protein. Altered expression levels of miR-107 influenced the migration and invasion behavior of MCF-7 and MDA-MB-231 cells.Our data indicate differential concentrations of plasma miR-16, miR-107, miR-130a and miR-146a in different breast cancer subtypes, suggesting a potential role of these miRs in breast cancer biology and tumor progression.

Decreased expression of microRNA-107 predicts poorer prognosis in glioma.

The expression level of microRNA-107 (miR-107) has been proved to be decreased in many human malignant cancers. Especially in glioma, accumulating evidence indicates that miR-107 may play important parts in cell proliferation, apoptosis, and invasion in glioma. However, its clinical significance in glioma has not been investigated. This study aims at investigating the relationship between miR-107 expression level and clinical significance and analyzing its value of miR-107 in valuing the prognosis of glioma patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of miR-107 in 80 glioma and 17 normal brain tissues. The results showed the miR-107 expression level in glioma tissues was significantly lower than those in normal brain tissues (p < 0.001). The decreased expression of miR-107 in glioma was positively associated with high WHO grade (p < 0.001), low Karnofsky performance score (KPS) (p < 0.001), and large tumor size (p < 0.001) and had a significant impact on overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) according to Kaplan-Meier survival with log-rank test. Finally, Cox regression analyses showed that low miR-107 expression (p < 0.001) might be an independent prognostic parameter to predict poor prognosis. In conclusion, it is the first data to prove that expression level of miR-107 may be a novel and valuable prognostic factor in glioma.

Molecular Mechanism for Hypertensive Renal Disease: Differential Regulation of Chromogranin A Expression at 3'-Untranslated Region Polymorphism C+87T by MicroRNA-107.

Chromogranin A (CHGA) is coreleased with catecholamines from secretory vesicles in adrenal medulla and sympathetic axons. Genetic variation in the CHGA 3'-region has been associated with autonomic control of circulation, hypertension, and hypertensive nephropathy, and the CHGA 3'-untranslated region (3'-UTR) variant C+87T (rs7610) displayed peak associations with these traits in humans. Here, we explored the molecular mechanisms underlying these associations. C+87T occurred in a microRNA-107 (miR-107) motif (match: T>C), and CHGA mRNA expression varied inversely with miR-107 abundance. In cells transfected with chimeric luciferase/CHGA 3'-UTR reporters encoding either the T allele or the C allele, changes in miR-107 expression levels had much greater effects on expression of the T allele. Cotransfection experiments with hsa-miR-107 oligonucleotides and eukaryotic CHGA plasmids produced similar results. Notably, an in vitro CHGA transcription/translation experiment revealed that changes in hsa-miR-107 expression altered expression of the T allele variant only. Mice with targeted ablation of Chga exhibited greater eGFR. Using BAC transgenesis, we created a mouse model with a humanized CHGA locus (T/T genotype at C+87T), in which treatment with a hsa-miR-107 inhibitor yielded prolonged falls in SBP/DBP compared with wild-type mice. We conclude that the CHGA 3'-UTR C+87T disrupts an miR-107 motif, with differential effects on CHGA expression, and that a cis:trans (mRNA:miR) interaction regulates the association of CHGA with BP and hypertensive nephropathy. These results indicate new strategies for probing autonomic circulatory control and ultimately, susceptibility to hypertensive renal sequelae.

Upregulation of MicroRNA-107 induces proliferation in human gastric cancer cells by targeting the transcription factor FOXO1

MicroRNA-107 (miR-107) has been demonstrated to regulate proliferation and apoptosis in many types of cancers. Nevertheless, its biological function in gastric cancer remains largely unexplored. Here, we found that the expression level of miR-107 was increased in gastric cancer in comparison with the adjacent normal tissues. The enforced expression of miR-107 was able to promote cell proliferation in NCI-N87 and AGS cells, while miR-107 antisense oligonucleotides (antisense miR-107) blocked cell proliferation. At the molecular level, our results further revealed that expression of FOXO1 was negatively regulated by miR-107. Therefore, the data reported here demonstrate that miR-107 is an important regulator in gastric cancer, which will contribute to a better understanding of the important mis-regulated miRNAs in gastric cancer.

Abstract 5292: MicroRNA signatures predictive of response to chemotherapy in mCRC.

Abstract MicroRNAs (miRNAs) are post-transcriptional regulators involved in numerous biological and pathological processes including colorectal cancer (CRC). From a clinical perspective, several studies have identified groups of miRNAs with potential utility for early diagnosis or prognostic stratification of CRC patients. However, very few have evaluated the potential ability of miRNA to predict response to selected chemotherapy regimens. The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC). We examined tumor expression levels of 667 miRNAs in the training cohort by TaqMan Low Density Arrays (TLDA). In training cohort (N=39), we identified a miRNA molecular signature with significant association in relevant clinical endpoints (objective response, progression-free and overall survival). In validation cohort (N=39), we validated significantly higher expression levels of miR-107, and miR99a* according to objective response to fluoropyrimidine-based regimens. These results support a substantial role for miRNAs in determining drug response, and highlight their potential value as biomarkers for personalized treatment strategies and as a novel class of therapeutic targets. Citation Format: Sonia Molina-Pinelo, Amancio Carnero, Fernando Rivera, Purificacion Estevez-Garcia, Jose M. Bozada, Maria L. Limon, Javier Gomez, Maria D. Pastor, Rocio Suarez, Luis G. Paz-Ares, Fernando de la Portilla, Andres Carranza, Isabel Sevilla, Luis Vicioso, Rocio Garcia Carbonero. MicroRNA signatures predictive of response to chemotherapy in mCRC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5292. doi:10.1158/1538-7445.AM2013-5292

MiR-107: a Toll-like receptor-regulated miRNA dysregulated in obesity and type II diabetes

miRNAs are small noncoding RNAs that act as regulators of gene expression. Dysregulation of miRNAs has been shown to contribute to multiple disease processes. It has become apparent that miRNAs play a key role in the innate immune response, whereby a large number of miRNAs have been demonstrated to be regulated by TLRs, key initiators of the innate immune response to infection. Recently, the LPS receptor, TLR4, has been shown to down-regulate miR-107 in macrophages. In addition, miR-107 has been demonstrated to be dysregulated in murine and rodent models of obesity and insulin resistance, respectively, with miR-107 contributing to both conditions. With obesity and inflammation being so intrinsically associated, the link between the miR-107 expression levels, inflammation, and insulin resistance may be of particular importance in metabolic diseases. The decrease in miR-107 in response to TLR4 may be an attempt to limit insulin resistance, a feature of obesity-related inflammation. If this process is impaired, disease, such as T2D, might persist. This review aims to discuss a possible link between the molecular phenomena of obesity and inflammation and the role that miR-107 may contribute to these processes.

Clinicopathological and prognostic significance of microRNA-107 and its relationship to DICER1 mRNA expression in gastric cancer

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.

MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations

Molecular classifications defining new tumor subtypes have been recently refined with genetic and transcriptomic analyses of benign and malignant hepatocellular tumors. Here, we performed microRNA (miRNA) profiling in two series of fully annotated liver tumors to uncover associations between oncogene/tumor suppressor mutations and clinical and pathological features. Expression levels of 250 miRNAs in 46 benign and malignant hepatocellular tumors were compared to those of 4 normal liver samples with quantitative reverse-transcriptase polymerase chain reaction. miRNAs associated with genetic and clinical characteristics were validated in a second series of 43 liver tumor samples and 16 nontumor samples. miRNA profiling unsupervised analysis classified samples in unique clusters characterized by histological features (tumor/nontumor, P < 0.001; benign/malignant tumors, P < 0.01; inflammatory adenoma and focal nodular hyperplasia, P < 0.01), clinical characteristics [hepatitis B virus (HBV) infection, P < 0.001; alcohol consumption, P < 0.05], and oncogene/tumor suppressor gene mutations [beta-catenin, P < 0.01; hepatocyte nuclear factor 1alpha (HNF1alpha), P < 0.01]. Our study identified and validated miR-224 overexpression in all tumors and miR-200c, miR-200, miR-21, miR-224, miR-10b, and miR-222 specific deregulation in benign or malignant tumors. Moreover, miR-96 was overexpressed in HBV tumors, and miR-126* was down-regulated in alcohol-related hepatocellular carcinoma. Down-regulations of miR-107 and miR-375 were specifically associated with HNF1alpha and beta-catenin gene mutations, respectively. miR-375 expression was highly correlated to that of beta-catenin-targeted genes as miR-107 expression was correlated to that of HNF1alpha in a small interfering RNA cell line model. Thus, this strongly suggests that beta-catenin and HNF1alpha could regulate miR-375 and miR-107 expression levels, respectively. Hepatocellular tumors may have a distinct miRNA expression fingerprint according to malignancy, risk factors, and oncogene/tumor suppressor gene alterations. Dissecting these relationships provides a new hypothesis to understand the functional impact of miRNA deregulation in liver tumorigenesis and the promising use of miRNAs as diagnostic markers.