MicroRNAs as biomarkers for early diagnosis, targeting and prognosis of prostate cancer.

Globally, prostate cancer (PC) is leading cause of cancer-related mortality in men worldwide. Despite significant advances in the treatment and management of this disease, the cure rates for PC remains low, largely due to late detection. PC detection is mostly reliant on prostate-specific antigen (PSA) and digital rectal examination (DRE); however, due to the low positive predictive value of current diagnostics, there is an urgent need to identify new accurate biomarkers. Recent studies support the biological role of microRNAs (miRNAs) in the initiation and progression of PC, as well as their potential as novel biomarkers for patients' diagnosis, prognosis, and disease relapse. In the advanced stages, cancer-cell-derived small extracellular vesicles (SEVs) may constitute a significant part of circulating vesicles and cause detectable changes in the plasma vesicular miRNA profile. Recent computational model for the identification of miRNA biomarkers discussed. In addition, accumulating evidence indicates that miRNAs can be utilized to target PC cells. In this article, the current understanding of the role of microRNAs and exosomes in the pathogenesis and their significance in PC prognosis, early diagnosis, chemoresistance, and treatment are reviewed.

Inflammation related miRNAs as an important player between obesity and cancers.

The growing trend in addition to their burden, prevalence, and death has made obesity and cancer two of the most concerning diseases worldwide. Obesity is an important risk factor for common types of cancers where the risk of some cancers is directly related to the obesity. Various inflammatory mechanisms and increased level of pro-inflammatory cytokines have been investigated in many previous studies, which play key roles in the pathophysiology and development of both of these conditions. On the other hand, in the recent years, many studies have individually focused on the biomarker's role and therapeutic targeting of microRNAs (miRNAs) in different types of cancers and obesity including newly discovered small noncoding RNAs (sncRNAs) which regulate gene expression and RNA silencing. This study is a comprehensive review of the main inflammation related miRNAs in obesity/obesity related traits. For the first time, the main roles of miRNAs in obesity related cancers have been discussed in response to the question raised in the following hypothesis; do the main inflammatory miRNAs link obesity with obesity-related cancers regarding their role as biomarkers? Graphical abstractConceptual design of inflammatory miRNAs which provide link between obesity and cancers.

A Genotype-First Approach for Clinical and Genetic Evaluation of Wolcott-Rallison Syndrome in a Large Cohort of Iranian Children With Neonatal Diabetes.

OBJECTIVE: Wolcott-Rallison syndrome (WRS) is an extremely rare autosomal recessive condition, characterized by permanent neonatal diabetes mellitus (PNDM) associated with skeletal dysplasia, growth retardation and liver dysfunction. WRS is caused by biallelic mutations in the gene encoding eukaryotic translation initiation factor 2alpha kinase 3 (EIF2AK3). METHODS: As part of a comprehensive study on clinical and genetic investigation of neonatal diabetes in an Iranian population, 60 unrelated Iranian subjects referred with PNDM were analyzed. All the probands were screened for KCNJ11, INS, ABCC8 and EIF2AK3 using a polymerase chain reaction-based sequencing approach. RESULTS: We identified 9 different variants in EIF2AK3 in 11 unrelated Iranian probands, of which 5 variants were shown to be novel and not reported previously. The diagnosis of WRS was made by molecular genetic testing and confirmed by clinical re-evaluation of the subjects. Clinical follow up of the affected individuals shows that in at least some of them, PNDM was associated with short stature, failure to thrive, neurodevelopmental delay, epilepsy and hepatic and renal dysfunction. There was a strong family history of neonatal diabetes in the families of the probands with a high mortality rate. CONCLUSION: WRS is a common cause of PNDM in children of consanguineous parents. Furthermore, clinical diagnosis of WRS would have been delayed or possibly missed without genetic testing because this study shows that the associated features of WRS might be obscured by a diagnosis of PNDM. Therefore EIF2AK3 should be considered for any infant and young child with PNDM, particularly if the parents are related.