In the development of the skeleton, the long bones are arising from the process of endochondral ossification (EO) in which cartilage is replaced by bone. This complex process is regulated by various factors including genetic, epigenetic, and environmental elements. It is recognized that DNA methylation, higher-order chromatin structure, and post-translational modifications of histones regulate the EO. With emerging understanding, non-coding RNAs (ncRNAs) have been identified as another mode of EO regulation, which is consist of microRNAs (miRNAs or miRs) and long non-coding RNAs (lncRNAs). There is expanding experimental evidence to unlock the role of ncRNAs in the differentiation of cartilage cells, as well as the pathogenesis of several skeletal disorders including osteoarthritis. Cutting-edge technologies such as epigenome-wide association studies have been employed to reveal disease-specific patterns regarding ncRNAs. This opens a new avenue of our understanding of skeletal cell biology, and may also identify potential epigenetic-based biomarkers. In this review, we provide an updated overview of recent advances in the role of ncRNAs especially focus on miRNA and lncRNA in the development of bone from cartilage, as well as their roles in skeletal pathophysiology.

Myosin VI, encoded by MYH6, is expressed dominantly in human cardiac atria and plays consequential roles in cardiac muscle contraction and comprising the cardiac muscle thick filament. It has been reported that the mutations in the MYH6 gene associated with sinus venosus atrial septal defect (ASD type III), hypertrophic (HCM) and dilated (DCM) cardiomyopathies. Two patients in an Iranian family have been identified who affected to Congenital Heart Disease (CHD). The male patient, besides CHD, shows that the thyroglossal sinus, refractive errors of the eye and mitral stenosis. The first symptoms emerged at the birth and diagnosis based on clinical features was made at about 5 years. The family had a history of ASD. For recognizing mutated gene (s), whole exome sequencing (WES) was performed for the male patient and variants were analyzed by autosomal dominant inheritance mode. Eventually, by several filtering processes, a mutation in MYH6 gene (NM_002471.3), c.3835C > T; R1279X, was identified as the most likely disease-susceptibility variant and then confirmed by Sanger sequencing in the family. The mutation frequency was checked out in the local databases. This mutation results in the elimination of the 660 amino acids in the C-terminal of Myosin VI protein, including the vital parts of the coiled-coil structure of the tail domain. Our study represents the first case of Sinus venosus defect caused directly by MYH6 stop codon mutation. Our data indicate that by increase haploinsufficiency of myosin VI, c.3835C > T mutation with reduced penetrance could be associated with CHD.

Background: Breast cancer (BC) is by far the most common malignancy among women. Epigenetic modulators, microRNAs in particular, may set stages for BC development and its progression. Herein, we aimed to assess the diagnostic potentiality of a signature of six miRNAs (i.e., hsa‐miR‐25‐3p, ‐29a‐5p, ‐105‐3p, ‐181b1‐5p, ‐335‐5p, and ‐339‐5p) in BC and adjacent non‐tumor tissues.Methods: A pair of 50 tumor and adjacent non‐tumor samples were taken from BC patients. The expression of each candidate miRNA was measured using quantitative reverse transcription PCR. To investigate the possible roles of each miRNA and their impressions on BC prognosis, in silico tools were used. Receiver operating characteristic (ROC) curves were performed to determine the diagnostic accuracy of each miRNA and the possible association of their expression with clinicopathological characteristics was analyzed.Results: Our findings showed the upregulation of hsa‐miR‐25‐3p, ‐29a‐5p, ‐105‐3p, and ‐181b1‐5p, and the downregulation of hsa‐miR‐335‐5p and ‐339‐5p in BC tumor compared to corresponding adjacent tissues. Except for hsa‐miR‐339‐5p, the up‐/down‐regulation of the candidate miRNAs was associated with TNM stages. Except for hsa‐miR‐105‐3p, each candidate miRNA was correlated with HER‐2 status. ROC curve analysis showed that the signature of six‐miRNA is a potential biomarker distinguishing between tumor and non‐tumor breast tissue samples.Conclusion: We showed that the dysregulation of a novel signature of six‐miRNA can be used as a potential biomarker for BC diagnosis.

Fra-1 (fosl1) belongs to the activator protein1 (AP-1) family inducing IL-11 expression in oxidative stress condition. IL-11 plays a pivotal role in protecting epithelial barriers integrity. In this study, we investigated the Fra-1 gene expression in the inflamed mucosa of patients with ulcerative colitis (UC) as well as its relation to IL-11 expression. We enrolled 20 patients and 20 healthy controls with definite UC based on the clinical criteria. Fra-1 gene expression in inflamed and non-inflamed colonic biopsies was determined by real-time polymerase chain reaction (RT-PCR). The IL-11 protein concentration was measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. Pearson correlation was applied to calculate the relation between Fra-1 and IL-11. An increased level of Fra-1 gene expression was observed in patients with mild ulcerative colitis. The protein concentration of IL-11 was also increased in mild UC patients. Conversely, a significant decrease of IL-11 protein level was detected in severe UC patients compared to control group. Oxidative stress in inflamed intestinal biopsies can induce fra-1 gene expression. Our findings suggest that Fra-1 transcription factor leads to the production of IL-11 protein in UC patients.