Good or not good: Role of miR-18a in cancer biology

miR-18a is a member of primary transcript called miR-17-92a (C13orf25 or MIR17HG) which also contains five other miRNAs: miR-17, miR-19a, miR-20a, miR-19b and miR-92a. This cluster as a whole shows specific characteristics, where miR-18a seems to be unique. In contrast to the other members, the expression of miR-18a is additionally controlled and probably functions as its own internal controller of the cluster. miR-18a regulates many genes involved in proliferation, cell cycle, apoptosis, response to different kinds of stress, autophagy and differentiation. The disturbances of miR-18a expression are observed in cancer as well as in different diseases or pathological states. The miR-17-92a cluster is commonly described as oncogenic and it is known as ‘oncomiR-1’, but this statement is a simplification because miR-18a can act both as an oncogene and a suppressor.In this review we summarize the current knowledge about miR-18a focusing on its regulation, role in cancer biology and utility as a potential biomarker

cfRNAs as biomarkers in oncology – still experimental or applied tool for personalized medicine already?

Currently, the challenges of contemporary oncology are focused mainly on the development of personalized medicine and precise treatment, which could be achieved through the use of molecular biomarkers. One of the biological molecules with great potential are circulating free RNAs (cfRNAs) which are present in various types of body fluids, such as blood, serum, plasma, and saliva. Also, different types of cfRNA particles can be distinguished depending on their length and function: microRNA (miRNA), PIWI-interacting RNA (piRNA), tRNA-derived RNA fragments (tRFs), circular RNA (circRNA), long non-coding RNA (lncRNA), and messenger RNA (mRNA). Moreover, cfRNAs occur in various forms: as a free molecule alone, in membrane vesicles, such as exosomes, or in complexes with proteins and lipids. One of the modern approaches for monitoring patient's condition is a "liquid biopsy" that provides a non-invasive and easily available source of circulating RNAs. Both the presence of specific cfRNA types as well as their concentration are dependent on many factors including cancer type or even reaction to treatment. Despite the possibility of using circulating free RNAs as biomarkers, there is still a lack of validated diagnostic panels, defined protocols for sampling, storing as well as detection methods.In this work we examine different types of cfRNAs, evaluate them as possible biomarkers, and analyze methods of their detection. We believe that further research on cfRNA and defining diagnostic panels could lead to better and faster cancer identification and improve treatment monitoring

YRNAs: New Insights and Potential Novel Approach in Head and Neck Squamous Cell Carcinoma

YRNAs are a class of non-coding RNAs that are components of the Ro60 ribonucleoprotein particle and are essential for initiation of DNA replication. Ro60 ribonucleoprotein particle is a target of autoimmune antibodies in patients suffering from systemic lupus erythematosus and Sjögren’s syndrome. Deregulation of YRNAs has been confirmed in many cancer types, but not in head and neck squamous cell carcinoma (HNSCC). The main aim of this study was to determine the biological role of YRNAs in HNSCC, the expression of YRNAs, and their usefulness as potential HNSCC biomarkers. Using quantitative reverse transcriptase (qRT)-PCR, the expression of YRNAs was measured in HNSCC cell lines, 20 matched cancer tissues, and 70 FFPETs (Formaline-Fixed Paraffin-Embedded Tissue) from HNSCC patients. Using TCGA (The Cancer Genome Atlas) data, an analysis of the expression levels of selected genes, and clinical-pathological parameters was performed. The expression of low and high YRNA1 expressed groups were analysed using gene set enrichment analysis (GSEA). YRNA1 and YRNA5 are significantly downregulated in HNSCC cell lines. YRNA1 was found to be significantly downregulated in patients’ tumour sample. YRNAs were significantly upregulated in T4 stage. YRNA1 showed the highest sensitivity, allowing to distinguish healthy from cancer tissue. An analysis of TCGA data revealed that expression of YRNA1 was significantly altered in the human papilloma virus (HPV) infection status. Patients with medium or high expression of YRNA1 showed better survival outcomes. It was noted that genes correlated with YRNA1 were associated with various processes occurring during cancerogenesis. The GSEA analysis showed high expression enrichment in eight vital processes for cancer development. YRNA1 influence patients’ survival and could be used as an HNSCC biomarker. YRNA1 seems to be a good potential biomarker for HNSCC, however, more studies must be performed and these observations should be verified using an in vitro model

Oncogenic Role of ZFAS1 lncRNA in Head and Neck Squamous Cell Carcinomas

Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Accordingly, here we investigate the biological role of ZFAS1 and its potential as a biomarker in HNSCC. Methods: The expression level of ZFAS1 in HNSCC cell lines was analyzed using qRT-PCR. Based on the HNSCC TCGA data, the ZFAS1 expression profile, clinicopathological features, and expression of correlated genes were analyzed in patient tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. The interaction between lncRNA:miRNA and miRNA:mRNA was tested using available online tools. All statistical analyses were accomplished using GraphPad Prism 5. Results: The expression of ZFAS1 was up-regulated in the metastatic FaDu cell line relative to the less aggressive SCC-25 and SCC-040 and dysplastic DOK cell lines. The TCGA data indicated an up-regulation of ZFAS1 in HNSCCs compared to normal tissue samples. The ZFAS1 levels typically differed depending on the cancer stage and T-stage. Patients with a lower expression of ZFAS1 presented a slightly longer disease-free survival and overall survival. The analysis of genes associated with ZFAS1, as well its targets, indicate that they are linked with crucial cellular processes. In the group of patients with low expression of ZFAS1, we detected the up-regulation of suppressors and down-regulation of genes associated with epithelial-to-mesenchymal transition (EMT) process, metastases, and cancer-initiating cells. Moreover, the negative correlation between ZFAS1 and its host gene, ZNFX1, was observed. The analysis of interactions indicated that ZFAS1 has a binding sequence for miR-150-5p. The expression of ZFAS1 and miR-150-5p is negatively correlated in HNSCC patients. miR-150-5p can regulate the 3′UTR of EIF4E mRNA. In the group of patients with high expression of ZFAS1 and low expression of miR-150-5p, we detected an up-regulation of EIF4E. Conclusions: In HNSCC, ZFAS1 displays oncogenic properties, regulates important processes associated with EMT, cancer-initiating cells, and metastases, and might affect patients’ clinical outcomes. ZFAS1 likely regulates the cell phenotype through miR-150-5p and its downstream targets. Following further validation, ZFAS1 might prove a new and valuable biomarker

lncRNA Expression after Irradiation and Chemoexposure of HNSCC Cell Lines

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world. To improve the quality of diagnostics and patients’ treatment, new and effective biomarkers are needed. Recent studies have shown that the expression level of different types of long non-coding RNAs (lncRNAs) is dysregulated in HNSCC and correlates with many biological processes. In this study, the response of lncRNAs in HNSCC cell lines after exposure to irradiation and cytotoxic drugs was examined. The SCC-040, SCC-25, FaDu, and Cal27 cell lines were treated with different radiation doses as well as exposed to cisplatin and doxorubicin. The expression changes of lncRNAs after exposure to these agents were checked by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Target prediction was performed using available online tools and classified into specific biological processes and cellular pathways. The results indicated that the irradiation, as well as chemoexposure, causes changes in lncRNA expression and the effect depends on the cell line, type of agents as well as their dose. After irradiation using the dose of 5 Gy significant dysregulation of 4 lncRNAs, 10 Gy-5 lncRNAs, and 20 Gy-3 lncRNAs, respectively, were observed in all cell lines. Only lncRNAs Zfhx2as was down-regulated in all cell lines independently of the dose used. After cisplatin exposure, 14 lncRNAs showed lower and only two higher expressions. Doxorubicin resulted in lower expressions of eight and increased four of lncRNAs. Common effects of cytotoxic drugs were observed in the case of antiPEG11, BACE1AS, PCGEM1, and ST7OT. Analysis of the predicted targets for dysregulated lncRNAs indicated that they are involved in important biological processes, regulating cellular pathways connected with direct response to irradiation or chemoexposure, cellular phenotype, cancer initiating cells, and angiogenesis. Both irradiation and chemoexposure caused specific changes in lncRNAs expression. However, the common effect is potentially important for cellular response to the stress and survival. Further study will show if lncRNAs are useful tools in patients’ treatment monitoring

IGFBP7 Concentration May Reflect Subclinical Myocardial Damage and Kidney Function in Patients with Stable Ischemic Heart Disease

The objective of this study was to determine the associations between insulin-like growth-factor-binding protein 7(IGFBP7) concentrations and concentrations of troponin T(TnT), N-terminal pro-B-type natriuretic peptide(NT-proBNP) and the parameters of kidney function in patients with stable ischemic heart disease(IHD). The IHD group consisted of 88 patients, and the population group comprised 66 subjects without a history of IHD. IGFBP7, TnT and NTproBNP concentrations were measured. The IGFBP7 value was considerably higher in the IHD group (1.76 ± 1 ng/mL vs. 1.43 ± 0.44 ng/mL, respectively, p = 0.019). Additionally, IHD subjects had a significantly higher concentration of TnT and NTproBNP. In both groups there was a significant correlation between IGFBP7 and serum parameters of kidney function (creatinine concentration: population gr. r = 0.45, p p p p p p 2 for the model 0.76). IHD patients presented significantly higher IGFBP7 concentrations than the population group. Elevated IGFBP7 levels are associated predominantly with markers of kidney function and myocardial damage or overload

Impact of Pulse Wave Velocity and Parameters Reflecting Android Type Fat Distribution on Left Ventricular Diastolic Dysfunction in Patients with Chronic Coronary Syndromes

Background: Left ventricular diastolic dysfunction (LVDD) is caused by a decreased left ventricle relaxation and is associated with an increased risk of symptomatic heart failure (HF) and excessive mortality. Aim: To evaluate the frequency and factors related to LVDD in the population with chronic coronary syndromes (CCS). Methods: 200 patients (mean age 63.18 ± 8.12 years, 75.5% male) with CCS were included. LVDD was diagnosed based on the recent echocardiography guidelines. Results: LVDD was diagnosed in 38.5% of CCS population. From the studied factors, after adjustment for age, sex, and N-terminal pro-brain natriuretic peptide (NT-proBNP), LVDD associated positively with android/gynoid (A/G) fat mass ratio, left ventricular mass index (LVMI), and negatively with Z-score and left ventricular ejection fraction (LVEF). In stepwise backward logistic regression analysis, the strongest factors associated with LVDD were pulse wave velocity value, handgrip strength and waist to hip ratio (WHR). Conclusions: LVDD is common among CCS patients and it is associated with parameters reflecting android type fat distribution regardless of NT-proBNP and high-sensitivity troponin T concentrations. Deterioration in diastolic dysfunction is linked with increased aortic stiffness independently of age and sex. Further studies evaluating the effects of increasing physical fitness and lowering abdominal fat accumulations on LVDD in CCS patients should be considered

ECG Indices Poorly Predict Left Ventricular Hypertrophy and Are Applicable Only in Individuals with Low Cardiovascular Risk

Background: Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular events. The electrocardiography (ECG) has poor sensitivity, but it is commonly used to detect LVH. Aim: To evaluate the diagnostic efficacy of known ECG indicators to recognize LVH in subgroups with different cardiovascular risk levels. Methods: 676 volunteers were included. Results: We found that 10.2% of the analyzed population had LVH based on echocardiography. Individuals with LVH were older, had a higher body mass index, higher systolic blood pressure, lower heart rate, higher parameters of insulin resistance, higher cardiovascular risk, and android-type obesity. Variables that remained independently associated with LVH were QRS duration, left atrial volume index, troponin T, and hemoglobin A1c. The receiver operating characteristics (ROC) curve analysis of the Sokolow–Lyon index did not show a significant predictive ability to diagnose LVH in the whole study population including all cardiovascular risk classes. The ROC curves analysis of Cornell and Lewis indices showed a modest predictive ability to diagnose LVH in the general population and in a low cardiovascular class. Conclusions: There is a need for new, simple methods to diagnose LVH in the general population in order to properly evaluate cardiovascular risk and introduce optimal medical treatment of concomitant disease