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Background: Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST) is a type of microsatellite instability that occurs in ∼60% of colorectal cancers (CRCs) and associated with MSH3 dysfunction. A 5-fluorouracil (5-FU)-related cytotoxicity is attenuated in MSH3-deficient colon cancer cells. Reported here is the predictive value of EMAST in CRCs with Stage II or III disease treated with 5-FU-based chemotherapy.Methods: EMAST status was analyzed in 157 patients with CRC with Stage II or III disease and MSH3 expression was analyzed using immunohistochemistry. The patients treated with 5-FU-based chemotherapy were studied in terms of the links of EMAST status with MSH3 expression, clinicopathological features, and overall survival (OS).Results: A total of 63 patients (40.1%) had EMAST positive (EMAST + ) CRC and 77 patients (49.0%) had low MSH3 expression. EMAST + tumors were associated with advanced TNM stage and poor and moderately differentiated tumor. EMAST CRC was more frequently observed in tumors with low expression of MSH3 in the nucleus (n = 53; 84.1%, p < .001). On multivariate analysis, patients with EMAST + status had a worse OS (hazard ratio: 2.489, 95% confidence interval [1.149-5.394], and p = .021).Worse OS in EMAST + patients who received 5-FU-based chemotherapy was significantly more common compared with EMAST − CRCs. Conclusion:There is a link between EMAST and reduced nuclear expression of MSH3. There is worse survival in patients with EMAST + CRC after 5-FU-based chemotherapy. According to our findings, adjuvant 5-FU-based chemotherapy might not be advantageous in EMAST + CRCs with Stage II or III disease.

MicroRNAs (miRNAs), have been documented to perform a key role in the pathogenesis of multiple sclerosis (MS), a chronic inflammatory and autoimmune disease. Recent studies have shown that single nucleotide polymorphism in the sequence of the miRNA may change their production and expression which can lead to miRNA dysfunction and pathogenicity. Some studies have reported the relationship between miRNA polymorphism and the increased risk of autoimmune disease. This study was conducted to investigate the association between mir155 rs767649, mir196a2 rs11614913 and mir23a rs3745453 polymorphism and the risk of multiple sclerosis in the Iranian MS patients in Isfahan. A population of 80 patients and the same number control were selected. After DNA extraction, genotyping was performed through tetra amplification refractory mutation system-PCR method (T ARMS PCR). The frequencies of TT, TC and CC genotypes of mir23a were 46, 35 and 20% in MS patients and 42, 14 and 24 in healthy subjects respectively. These results showed that individuals carrying the genotypes of rs3745453 TC had a 2.3-fold increased risk of MS (OR=2.3, p=0.048). There was no significant difference between genotypes and allele frequency of mir155 and mir196a2 in patients and healthy controls (p>0.05). Our findings specified that CT heterozygosity in mir23a gene significantly related with risk of MS. Unlike mir155 and mir196a2, mir23a rs3745453 may have contributed to the etiology of MS in Isfahan patients. However, extensive studies are required to gain more reliable and authentic results.

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