Competing endogenous RNAs (ceRNAs) are RNA transcripts which can communicate with each other by decreasing targeting concentration of micro-RNA (miRNA) with the derepression of other messenger RNAs (mRNAs) having the common miRNA response elements (MREs). Oncocers are ceRNAs taking crucial roles in oncogenic pathways processed in many types of cancer, and this study analyzes oncocer-mediated cross-talk by sponging microRNAs (miRNAs) in these pathways. While doing this, breast, liver, colon, prostate, gastric, lung, endometrium, thyroid and epithelial cancers and melanoma, rhabdomyosarcoma, glioblastoma, acute promyelocytic leukemia, retinoblastoma, and neuroblastoma were analyzed with respect to ceRNA-based carcinogenesis. This study defines, firstly, oncocers in the literature and contains all oncocer-related findings found up to now. Therefore, it will help to increase our comprehension about oncocer-mediated mechanisms. Via this study, a novel perspective would be produced to make clear cancer mechanisms and suggest novel approaches to regulate ceRNA networks via miRNA competition for cancer therapeutics. Graphical Abstract Multiple RNA transcripts have common MREs for the similar miRNA in their 3'-untranslated regions (3'-UTRs). Upregulation of ceRNAs rises the abundance of specific MREs and shifts the miRNA pool distribution, as a result, leading to the increased expression of target mRNA. The depot of genomic mutations and epigenetic alterations changing gene function and expression causes cancers. Herewith, genome-based somatic base-pair mutations, DNA copy number alterations, chromosomal translocation, also transcript fusions, alternative splicing are usually seen in cancer situations. Consequently, such cases causing changed UTR expression in transcripts influence the levels of MRE or present new MREs into the cells. Alterations in MREs of ceRNAs affect the capability of a specific mRNA transcript to attach or titrate miRNAs. As a result, the disturbed ceRNA network can lead to diseases and cancers. As a new term in RNA world, oncocers-the name for ceRNAs taking crucial roles in oncogenic pathways-are processed in many types of cancer, and oncocer-mediated cross-talk are analyzed by sponging miRNAs in these pathways.
MicroRNAs can regulate many biological functions. miR-122-5p has a tumor suppressor function through different molecular pathways. Also, our second hit, ADAM10, targeted by miR-122-5p, is a major determinant of HER2 shedding causing that trastuzumab cannot bind to HER2 receptors. Therefore, our analysis upon ADAM10 expression and miR-122-5p was a good point to understand molecular mechanism of breast cancer. In our study, we investigated the expression profiles of miR-122-5p and its target ADAM10 in 71 breast cancer patients. Immunohistochemical analysis of ER, PR and HER2 gene products was used to categorize tumors in patients. Expression data and immunohistochemical findings were evaluated to comment on the relationship between miR-122-5p and ADAM10. ADAM10 expression was higher in tumor than that of normal tissue but miR-122-5p expression was lower in tumor than that of normal tissue. The expression pattern in HER2+ patients was reverse of the overall result. It can be explained like that miR-122-5p expression increases especially in HER2+ cancer cell to suppress ADAM10 shedding activity on HER2 receptor. However, increase in expression of tumor suppressor miR-122-5p is not enough to inhibit ADAM10. All in all, we can think miR-122-5p as potential regulator of ADAM10 and trastuzumab resistance. Since if we increase miR-122-5p activity together with trastuzumab administration, then HER2+ breast cancer cells may overcome trastuzumab resistance by inhibiting ADAM10 shedding activity on HER2 receptors and increase the efficiency of trastuzumab.
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression, involved in the silencing of messenger RNA (mRNA) translation. The importance of miRNA signatures in disease screening, prognosis, and progression of different tumor types and subtypes is increasing. miRNA expression levels change depending on numerous factors. In this review, we are describing the circumstances under which miRNA levels can change, these are named 'levels' of heterogeneity of miRNAs. miRNAs can have oncogenic, tumor suppressive, or both roles depending on tumor type and target mRNA whose translation they silence. The expression levels of a single miRNA may vary across different cancer types and subtypes, indicating that a miRNA signature may be tissue specific. miRNA levels of expression also vary during disease formation and propagation, indicating the presence of a time profile for their expression. The complexity of the miRNA-mRNA interference network mirrors different genetic and epigenetic changes that influence miRNA and mRNA availability to each other, and hence, their binding ability. The potential role of miRNAs as biomarkers is two-fold; first, for monitoring of the phases of cancer pathogenesis, and second, to characterize the particular type/subtype of cancer. It is important that a particular miRNA should be characterized by examining as many types and subtypes of cancers as are available, as well as being extracted from different types of samples, in order to obtain a complete picture of its behavior and importance in the disease pathology.
Familial mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder (MIM# 249100), particularly common in populations of Mediterranean extraction. MEFV gene, responsible for FMF, encoding pyrin has recently been mapped to chromosome 16p13.3. In the present study, 3,341 unrelated patients with the suspicion of FMF in south-east part of Turkey between the years 2009 and 2013 were enrolled and genomic sequences of exon 2 and exon 10 of the MEFV gene were scanned for mutations by direct sequencing. We identified 43 different type of mutations and 9 of them were novel. DNA was amplified by PCR and subjected to direct sequencing for the detection of MEFV gene mutations. Among the 3,341 patients, 1,598 (47.8 %) were males and 1,743 (52.1 %) were females. The mutations were heterozygous in 806 (62.3 %), compound heterozygous in 188 (14.5 %), homozygous in 281 (21.8 %) and mutations had complex genotype in 17 (1.32 %) patients. No mutation was detected in 2,051 (61.4 %) patients. The most frequent mutations were M694V, E148Q, M680I(G/C) and V726A. We could not find any significant differences between the two common mutations according to the gender. Molecular diagnosis of MEFV is a useful tool in clinical practice, thus a future study relating to genotype/phenotype correlation of FMF in more and larger group in Turkish population involving the whole MEFV gene mutations is necessary.
Standard cancer therapies for solid malignancies, such as chemotherapy and radiotherapy, are not target specific against cancer cells and are often not fully efficacious. Chemotherapy and radiotherapy may cause side effects, and the need to develop additional strategies for cancer treatment is urgent. MicroRNAs (miRNAs) are small non-coding RNAs with heterogeneous functions and have been described in almost every known cancer model. Besides their basic tumor-suppressive and oncogenic functions, they also have the potential to modulate chemotherapy and radiotherapy and to be manipulated with chemical compounds to make them chemically suitable for efficient delivery to cancer cells. It has been suggested that the level of expression of specific miRNAs could increase treatment efficacy by determining the stage of chemotherapy/radiotherapy sensitivity. Application of miRNAs alone or in combination with standard therapeutic strategies may significantly improve the success of cancer treatments in the future.
Immune thrombocytopenic purpura (ITP) is a commonly acquired autoimmune bleeding disorder in children. MicroRNAs (miRNAs) are small RNAs which are found in cells and circulation, and play a role in protein synthesis and regulation. In this study, we aimed to determine a biomarker for childhood ITP comparing the plasma miRNA levels of children having ITP with healthy children. A total of 86 patients with ITP and 56 healthy children followed up by the Department of Pediatric Hematology and Oncology in University of Gaziantep since July 2011 were enrolled in the study. The 86 patients with ITP were evaluated in two groups as 43 acute ITP (aITP) and 43 chronic ITP (cITP) patients. Plasma expression levels of 379 miRNAs were investigated by RT-PCR (quantitative RT-PCR) technique and they were compared between aITP, cITP, and control groups. For all miRNAs, the average of raw quantification cycle values of three groups separately in the analysis chip was accepted as the reference gene value, and normalization was done according to this value. Statistically significant differences were detected in seven miRNAs (miR-302c-3p, miR-483-5p, miR-410, miR-544a, miR-302a-3p, miR-223-3p, and miR-597) investigated between the groups with respect to the expression levels. The expression rates were found to be over 95% in miR-302c-3p and miR-483-5p, over 75% in miR-410, and over 40% in miR-544, miR-302a-3p, and miR-223-3p in all three groups. The detection of significant differences between plasma miRNA levels of aITP and cITP patients and healthy children may provide useful information in the prediction of the course of disease, determination of disease etiopathogenesis, and the development of new therapeutic modalities.
MicroRNAs (miRNAs) are important factors during tumorigenesis by affecting posttranscriptional gene expression. miRNA 204 (miR-204) is a miRNA frequently investigated in different types of cancers. According to literature, autophagy has dual roles in cancer, acting as both a tumor suppressor and cell survival agent. Also, the current data suggests that autophagy is activated in human colorectal cancer cells and enhances the aggressiveness of human colorectal cancer cells. So, our aim is to investigate potential effect of miR-204-5p on colorectal cancer by associating its expression with autophagy-related targets of miR-204-5p. This is the first miRNA study conducted on patients with colorectal cancer and healthy subjects and also to search the relation of miR-204-5p with clinicopathological factors and survival. Sixty-six patients with colorectal cancer and healthy subjects without any known chronic disease were enrolled into our study. Total miRNA was isolated from paraffin-embedded tissues of all patients' cancerous and normal tissues, and healthy subjects. cDNAs were obtained from this miRNAs by reverse transcriptase method, and miR-204-5p relative expression levels were detected by qRT-PCR method. Patients were divided into two groups according to median relative expression levels of miR-204-5p, as low- and high-expression group. Relation of miR-204-5p with clinicopathological factors and overall survival was also investigated. Medians of miR-204-5p relative expression levels in cancerous and normal tissues of patients were found as 0.00235 and 0.00376, respectively. The difference between two groups was not statistically significant (p = 0.11). Nonetheless, median of miR-204-5p relative expression levels in healthy subjects were found as 0.00135, and the difference between patient with cancer and healthy subjects and between normal tissues of patients and healthy subjects were statistically significant (p = 0.021 and p = 0.0005, respectively). There were 32 patients (48.5 %) showing high expression and 34 patients (51.5 %) showing low expression according to miR-204-5p relative expression levels. There were no statistically significant relation between clinicopathologic features and miR-204-5p relative expression levels. We also investigated the relation between miR-204-5p relative expression levels and overall survival, and no statistically significant relation was found between them (p = 0.462). The absence of any significant difference between tumor and non-tumor samples, low sample size, and performance at just one center are the limitations of our study. In opposition to literature, miR-204-5p is overexpressed in colorectal cancer patients as compared with healthy subjects and this situation is not associated with clinicopathological factors and overall survival. This may be explained by the fact that miR-204-5p increases in colorectal cancer cases in order to inhibit increased activity of LC3B-II in autophagy and Bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor.
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