Dysregulation of miR-193a serves as a potential contributor to MS pathogenesis via affecting RhoA and Rock1.

BACKGROUND: Multiple sclerosis (MS) is one of the most common neurological diseases that cause chronic inflammation of the central nervous system and demyelination of the myelin sheath. At present, microRNAs (miRNAs) are considered not only a diagnostic and prognostic indicator of diseases but also a new goal in gene therapy. This study aims to find a simple, non-invasive, valuable biomarker for early detection and potential treatment of MS. METHODS: In the present study, 30 patients with MS were included. The qRT-PCR method was performed to evaluate the expression level of miR-193a, RhoA, and ROCK1. Besides, western blotting was performed to determine the expression level of RhoA and ROCK1 at protein levels. Moreover, we aimed to clarify the possible correlation between miR-193a-5p and its-regulated target genes so that miR-193a-5p mimic was transfected into MS-derived cultured PBMSs, and the expression level of RhoA and ROCK1 were then evaluated by qRT-PCR and Western blotting. In the final step, the correlation between miR-193a-5p and clinicopathological features of patients was investigated. RESULTS: Results showed that miR-193a was decreased while RhoA and ROCK1 were up-regulated in PBMCs obtained from patients with MS compared to the control group. It was also revealed that miR-193a transfection reduced RhoA and ROCK1 expression at mRNA and protein levels. The results from the Chi-square analysis showed that down-regulation of miR-193a was associated with increased CRP level, CSF IgG positivity, and MSSS (Multiple Sclerosis Severity Score), suggesting miR-193a is a potential diagnostic and prognostic indicator. CONCLUSION: We implied that miR-193a could modulate RhoA and ROCK 1 expression in MS patients, in which its down-regulation leads to increased expression of RhoA and ROCK1 and poor prognosis of patients with MS. Therefore, miR-193a and its associated targets could serve potential prognostic, diagnostic, and therapeutic efficacy in MS patients.

DNMT3B -149 C>T and -579 G>T Polymorphisms and Risk of Gastric and Colorectal Cancer: a Meta-analysis.

BACKGROUND: Numerous studies have investigated associations of DNA methyltransferase (DNMT) -149 C>T and -579 G>T polymorphisms with gastric cancer (GC) and colorectal cancer (CRC) susceptibility; however, the findings are inconsistent prompting the present meta-analysis. MATERIALS AND METHODS: Related studies were identified from PubMed, Google scholar, and SID until 10 October 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. RESULTS: Eleven studies were included based on the search criteria for CRC and GC related to the DNMT3B 149 C>T (3,353 cases and 4,936 controls) and DNMT3B 579 G>T (1,387 cases and 2,064 controls) polymorphisms. There was no significant association overall between DNMT3B -149 and 579 polymorphisms and the risk of cancer. In the stratified analysis by cancer type, DNMT3B 579G>T polymorphism was associated with the risk of CRC and GC. While the DNMT3B -149C/T polymorphism was related with a significantly increased risk of CRC in two tested models, dominant (GG+GT vs. TT: OR 0.51, 95 % CI 0.38-0.69; P = 0.00, Pheterogeneity=0.69, I2= 0 %) and heterozygote (GT vs. TT: OR 0.50, 95 % CI 0.37-0.69; P=0.00, Pheterogeneity=0.41, I2= 0 %), no evidence of any association with GC risk was observed as in the pooled analyses. CONCLUSIONS: More studies are needed to assess associations of DNMT3B -149C/T and DNMT3B 579G>T polymorphisms with cancer in different ethnicities with large population sizes to generate comprehensive conclusions.