MicroRNA - Volume 8, Issue 2, 2019

Growing evidence propose an association between miRNA polymorphisms and cancer susceptibility. This study aimed to examine the impact of miR-605 rs2043556 polymorphism on cancer risk through a meta-analysis based on 3198 cancer cases and 4943 controls. Eligible studies were retrieved by searching Web of Science, PubMed, Scopus, and Google Scholar databases up to August 27, 2018. The pooled Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were calculated using a random-effect model to estimate the strength of association between rs2043556 variant of miR-605 and cancer risk. Overall, no significant association was found between miR-605 rs2043556 polymorphism and cancer risk in heterozygous codominant (OR=0.93, 95% CI=0.76-1.13, p=0.44, AG vs. AA), homozygous codominant (OR=1.01, 95%CI=0.78-1.30, p=0.94, GG vs. AA), dominant (OR=0.95, 95% CI=0.79-1.13, p=0.55, AG+GG vs. AA), recessive (OR=1.07, 95%CI=0.84-1.38, p=0.57, GG vs. AG+AA), overdominant (OR=0.93, 95% CI=0.76-1.12, p=0.43, AG vs. GG+AA), and allele (OR=0.98, 95% CI=0.87-1.10, p=0.73, G vs. A) genetic models tested. Stratified analysis by cancer type revealed that the rs2043556 variant was not associated with digestive tract cancer, breast cancer, gastric cancer as well as lung cancer. Taken together, the findings of this meta-analysis did not support an association between miR-605 rs2043556 polymorphism and cancer susceptibility.

Objective: The study aims to review the recent data considering the expression profile and the role of microRNAs in breast tumorigenesis, and their impact on -the vital for breast cancer progression- angiogenesis. Methods: PubMed was searched for studies focused on data that associate microRNA with breast cancer, using the terms ''breast”, “mammary gland”, “neoplasia'', “angiogenesis” and ''microRNA'' between 1997-2018. Results: Aberrant expression of several circulating and tissue miRNAs is observed in human breast neoplasms with the deregulation of several miRNAs having a major participation in breast cancer progression. Angiogenesis seems to be directly affected by either overexpression or down regulation of many miRNAs, defining the overall prognostic rates. Many miRNAs differentially expressed in breast cancer that reveal a key role in suppression - progression and metastasis of breast cancer along with the contribution of the EGF, TNF-a and EGF cytokines. Conclusion Angiogenesis has proven to be vital for tumor development and metastasis while microRNAs are proposed to have multiple biological roles, including participation in immunosuppressive, immunomodulatory and recent studies reveal their implication in angiogenesis and its possible use as prognostic factors in cancer Even though larger studies are needed in order to reach safe conclusions, important steps are made that reveal the connection of serum microRNA expression to the angiogenic course of breast cancer, while miRNAs could be potential prognostic factors for the different breast cancer types.

Background: Early diagnosis is an important factor to improve the survival of Invasive Cervical Cancer (ICC) patients. Molecular biomarkers such as micro RNA (miRNA) can be used in the early detection of ICC. The expression of miR-21 and miR-29a are deregulated in many types of human cancers. Objective: The aim of this study was to investigate the differences in miR-21 and miR-29a expression patterns in the Human Papilloma Virus (HPV) infection and various grades of cervical cancer among Iranian women. Methods: Small RNAs were extracted from positive for HPV, cervical cancer and healthy samples from 43, 50 and 46 individuals, respectively. Expression levels of miR-21 and miR-29a were analyzed by SYBR Green real-time RT-PCR using specific primers, and 5s rRNA as the internal reference gene. Results: Results have shown a significant increase in miR-21 and decrease in miR-29 in cancerous samples in comparison with the control groups (P < 0.0001). Conclusion: This study illustrated that miR-21 and miR-29a could be operated as an oncogene and tumor-suppressor in cervical cancer progression. More studies are needed to demonstrate the role of miR-21 and miR-29a as potential biomarkers for the diagnosis of cervical cancer in future investigations.

Background: The Ketogenic Diet (KD) promotes metabolic changes and optimizes energy metabolism. It is unknown if microRNAs (miRs) are influenced by KD in obese subjects. The screening of circulating miRs was performed with the FDA approved platform n-counter flex and blood biochemical parameters were dosed by ADVIA 1800. Objectives: The aim of this study was to evaluate mir profile under 6 weeks of biphasic KD in obese subjects. We enrolled 36 obese subjects (18 females and 18 males) in stage 1 of Edmonton Obesity Staging System (EOSS) parameter. Result: Any correlation was found between biochemical parameter and three miRs, hsa-let-7b-5p, hsa-miR-143-3p and hsa-miR-504-5p influenced in an equal manner in both sexes. The KD resulted safe and ameliorate both biochemical and anthropometric factors in obese subjects re-collocating them into stage 0 of EOSS parameters. Conclusion: The miRs herein identified under KD might be a useful tool to monitor low carbohydrate nutritional regimens which reflect indirectly the regulatory biochemical mechanisms and cell signaling that orchestrate metabolic and signaling pathways.

Background: Atrial Fibrillation (AF) in patients without concomitant cardiovascular pathophysiological disease, is called idiopathic Atrial Fibrillation (iAF). Nonetheless, iAF patients have often times subclinical coronary (micro) vascular dysfunction and, particularly in women, a higher prevalence of subsequent cardiovascular comorbidities. Previously, we identified a plasma miRNA association with diabetes and microvascular injury in Diabetic Nephropathy (DN) patients. Therefore, in this study we assessed whether plasma levels of these diabetic, microvascular injury associated miRNAs reflect microvascular integrity in iAF patients, associated with the presence of paroxysmal arrhythmia or instead are determined by concealed coronary artery disease. Methods: Circulating levels of a pre-selected set of diabetic, (micro) vascular injury associated miRNAs, were measured in 59 iAF patients compared to 176 Sinus Rhythm (SR) controls. Furthermore, the presence of coronary artery and aortic calcification in each patient was assessed using Cardiac Computed Tomography Angiography (CCTA). Results: Paroxysmal arrhythmia in iAF patients did not result in significant miRNA expression profile differences in iAF patients compared to SR controls. Nonetheless, coronary artery calcification (CAC) was associated with higher levels of miRNAs-103, -125a-5p, -221 and -223 in men. In women, CAC was associated with higher plasma levels of miRNA-27a and miRNA-126 and correlated with Agatston scores. Within the total population, ascending Aortic Calcification (AsAC) patients displayed increased plasma levels of miRNA-221, while women, in particular, demonstrated a Descending Aorta Calcification (DAC) associated increase in miRNA-212 levels. Conclusions: Diabetic microvascular injury associated miRNAs in iAF are associated with subclinical coronary artery disease in a sex-specific way and confirm the notion that biological sex identifies iAF subgroups that may require dedicated clinical care.

Background: MicroRNAs (miRNAs) are a class of small non-coding, endogenous RNAs that regulate gene expression at post-transcriptional level. In plants, miRNAs are usually of 18-24 nucleotide in length and play humongous role by aiding in development, growth, defense, biotic and abiotic stress responses, etc. Objective: Arachis hypogaea is an economically important oil seed crop and human dietary source cultivated mostly in tropical and subtropical regions. In the present study, an initiative was taken to uncover miRNAs, their targets and functions in this important plant species. Method: Comparative genomics strategy coupled with bioinformatics approaches was deployed for the identification of miRNAs, their corresponding targets and functions by exploiting biological databases and tools. Results: The study was able to identify 34 conserved miRNA candidates, belonging to 17 miRNA families, contributed by 23 and 3 precursor miRNAs from A. hypogaea Expressed Sequence Tags (EST) and Genome Survey Sequences (GSS), respectively. As well, 495 EST and 917 unigene sequences were predicted as targets for the identified miRNAs. Herein, psRNAtarget server and TargetFinder tool were used to predict unigene targets, whereas comparative genomics strategy was used for identifying EST targets. Functional annotation of the identified targets revealed that the identified miRNAs regulate mRNAs that participate in key biological and metabolic processes. Pathway enrichment analysis using KEGG database also revealed that they regulate important metabolic pathways including antibiotic biosynthesis, biosynthesis of unsaturated fatty acids, amino acids metabolism and flavonoid biosynthesis. Conclusion: The outcome of the study would aid experimental biologists to focus on these miRNAs to facilitate improved crop development and yield.

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory and autoimmune disease leading to bones and joints destruction. It is one of the major causes of lifetime disability and mortality among humans in the developing and developed countries. It was evident that epigenetic dysregulation is related to the pathogenesis of RA. MicroRNAs (miRNAs) are small non-coding RNAs that are epigenetic regulators for diverse biological processes and also provided novel molecular insights in the formation of arthritis. Objective: The influences of miRNAs in the alteration of gene regulation during the pathogenesis of arthritis were exposed in recent years. Method: The computational approach to identify miRNA through EST-based homology is more powerful, economical and time-efficient. In this study, we applied EST-based homology search to identify miRNAs responsible for the development of arthritis in human beings. Results: Our study on 36519 ESTs in human RA condition revealed the expression of four miRNAs, HSA-miR-198, HSA-miR-4647, has-miR-7167-5p and has-miR-7167-3p. The present study is the first report about has-miR-7167 that was homologous to Macaca mulatta. Conclusion: The predicted targets of these identified miRNAs revealed many biological functions in the pathogenesis of RA. Further elaborated studies on these miRNAs will help to understand their function in the development of RA and the use of miRNAs as therapeutic targets in the future.

Background: HER2 positive Breast Cancers (BC) have aggressive behavior and poor prognosis. Previously, we have identified miR-342-5p as an upstream regulator of HER2 signaling, as well as inhibitor of HER2 positive BC cell line growth. Objective: Here, we aimed to further investigate the molecular mechanisms behind miR-342-5pinduced HER2 pathway deregulation. Method: Two HER2 amplified breast cancer cell lines were transiently transfected with miR-342-5p mimic or negative control, and gene expression was analyzed by Agilent microarrays. Three clinical datasets with BC patients were used to identify correlations between candidate genes and miR-342- 5p, and associations with survival. Results: Pathway analyses of all deregulated genes revealed a significant suppression of the HER2 downstream pathways ERK/MAPK and SAPK/JNK, whereas the miR-342-5p predicted target genes were enriched for pathways associated with cell motility.Biological functions linked to mitochondrial stability were ranked among the top toxicological functions in both gene lists. Among the most deregulated genes, Cytochrome B5 Reductase 3 (CYB5R3) and Rap Guanine Nucleotide Exchange Factor 6 (RAPGEF6) significantly anticorrelated and correlated, respectively, with miR-342-5p in all three clinical BC datasets. Low CYB5R3 levels and high RAPGEF6 levels were significantly associated with survival, although this was not directly associated with HER2 expression. Conclusion: Our data suggest that miR-342-5p overexpression in HER2 positive BC cell lines elicits broad effects on HER2 downstream signaling, cell motility and mitochondrial stability. Together these effects may render cells less proliferative and more sensitive to cellular stress.

Background: The discovery that a plant microRNA (miRNAs) from rice (Oryza sativa miR168a) can modify post-transcriptional expression of the mammalian. Low-Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) gene highlights the potential for cross-kingdom miRNAmRNA interactions. Objective: To investigate whether common variants of the conserved miR168a family have the capability for similar cross-kingdom regulatory functions, we selected sequences from three dietary plant sources: rice (Oryza sativa), tomato (Solanum lycopersicum), apple (Malus domestica) and compared their ability to regulate human LDLRAP1 expression. Methods: Target prediction software intaRNA and RNAhybrid were used to analyze and calculate the energy and alignment score between the miR168a variants and human LDLRAP1 mRNA. An in vitro cell-based Dual-Luciferase® Reporter Assay (pmirGLO, Promega), was then used to validate the miRNA-mRNA interaction experimentally. Results: Computational analyses revealed that a single nucleotide difference at position 14 (from the 5’ end of the miRNA) creates a G:U wobble in the miRNA-mRNA duplex formed by tomato and apple miR168a variants. This G:U wobble had only a small effect on the free energy score (-33.8–34.7 kcal/mol). However, despite reasonable hybridization energy scores (<-20 kcal/mol) for all miR168a variants, only the rice miR168a variant lacking a G:U wobble significantly reduced LDLRAP1 transcript expression by 25.8 + 7.3% (p<0.05), as measured by relative luciferase activity. Conclusion: In summary, single nucleotide differences at key positions can have a marked influence on regulatory function despite similar predicted energy scores and miRNA-mRNA duplex structures.