International Journal of Molecular and Cellular Medicine
Volume:8 Issue: 30, Spring 2019

Gastric cancer (GC) is one of the most common types of cancer and the second leading cause of cancer-associated mortality. Identification of novel biomarkers is critical to prolonging patient survival. MicroRNAs (miRNAs) proved to play diverse roles in the physiological and pathological state in cancers including GC. Herein we were aimed at performing a meta-analysis on miRNA profiling studies that used microarray platforms. Relevant studies were retrieved from PubMed and GEO databases. We used the robust rank aggregation to perform the meta-analysis. Moreover, for meta-signature miRNAs target genes, we performed pathway enrichment and GO molecular function enrichment analysis. A total of 19 upregulated miRNAs and seven downregulated miRNAs in GC samples were identified. However, only three upregulated and one downregulated miRNA reached statistical significance after multiple test correction. Here we showed that hsa-miR-21-5p, hsa-miR-93-5p, hsa-miR-25-3p, and hsa-miR-375 are differentially expressed in GC samples.

Early diagnosis of prostate cancer (PCa) as the second most common cancer in men is not associated with precise and specific results. Thus, alternate methods with high specificity and sensitivity are needed for accurate and timely detection of PCa. MicroRNAs regulate the molecular pathways involved in cancer by targeting multiple genes. The aberrant expression of the microRNAs has been reported in different cancer types including PCa. In this bioinformatics study, we studied differential expression profiles of microRNAs and their target genes in four PCa gene expression omnibus (GEO) databases. PCa diagnostic biomarker candidates were investigated using bioinformatics tools for analysis of gene expression data, microRNA target prediction, pathway and GO annotation, as well as ROC curves. The results of this study revealed significant changes in the expression of 14 microRNAs and 40 relevant target genes, which ultimately composed four combination panels (miR-375+96+663/miR-133b+143-3p+205/ C2ORF72+ENTPD5+GLYAT11/LAMB3+NTNG2+TSLP) as candidate biomarkers capable to distinguish between PCa tumor samples and normal prostate tissue samples. These biomarkers may be suggested for a more accurate early diagnosis of PCa patients along with current diagnostic tests.

Circulating microRNAs have been recognized as promising biomarkers for the detection of lung cancer. The objective of this study was to evaluate miR-10b, miR-1 and, miR-30a in the plasma samples of lung cancer patients to confirm any possible relevance in the early detection of lung cancer. Plasma samples from 47 non-small-cell lung cancer patients and 41 cancer-free subjects were evaluated for selected microRNAs using the real-time PCR method. To evaluate the tobacco smoking effects on microRNAs expression, the studied groups were categorized into two subgroups: never-smokers and smokers. MiR-1/miR-30a expression levels were significantly reduced in lung cancer, while the miR-10b level was significantly elevated. We found that smoking had significant effects on the levels of circulating microRNAs in the smokers of the cancer-free group (a significant up-regulation of miR-10b and significant down-regulation of miR-1/miR-30a), and lung cancer patients (a significant elevation of miR-10b). Receiver operating characteristic curve analysis showed that miR-10b with an area under the curve of 0.861, and miR-1/miR-30a with values of0.905 and 0.889 for the same parameter, could distinguish non-small-cell lung cancer patients from cancer-free subjects. Our findings demonstrated significant differences in the expression of microRNAs in lung cancer and the considerable effects of smoking on microRNAs levels. Area under curve analysis showed that miR-10b with 78% sensitivity/78% specificity, miR-1 with 95% sensitivity/80% specificity and miR-30a with 87% sensitivity/83% specificity,might be good (miR-10b/miR-30a) and excellent (miR-1) markers for lung cancer detection.

Inorganic arsenicals are worldwide environmental contaminants that affect molecular characteristics in biological systems and lead to genomic and epigenomic instability as well as epithelial mesenchymal transition (EMT). In this study, we aimed to investigate whether low levels of sodium arsenite (iAsIII) can influence EMT and genomic instability through microsatellite analysis. We have also determined epigenomic instability by investigating the methylation status of SEPT9 tumor marker in colorectal cancer (CRC) cell lines, Caco2 and HCT116, which were treated with iAsIII to assess IC50s. Short-term and long-term exposure to low concentrations (1 µM and 0.1 µM) of iAsIII in two separate experiments was implemented to analyze EMT, microsatellite status and the methylation pattern of SEPT9 promoter. As expected, after 20 days of exposure to iAsIII, the expression of CDH1 was significantly decreased while the expression of CDH2, FIB1 and VIM was increased in Caco2 and HCT116, a finding that confirmed EMT induction. However, there was no detectable alteration in the size of microsatellites. As for the methylation pattern, SEPT9 promoter was hypomethylated as a result of long-term exposure to 0.1 µM iAsIII in Caco2. Long-term exposure of HCT116 to both concentrations could induce hypomethylation of SEPT9 promoter. Our findings indicate no linkage between EMT induction and microsatellite status in iAsIII-treated CRC cell lines. For the first time, the current study has shown that the induction of EMT by iAsIII is linked with SEPT9 promoter hypomethylation in Caco2 and HCT116 in a concentration- and time-dependent pattern.

Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide, which is used in many plastic industries. The present study aimed to evaluate the effect of BPA on cognitive functions and oxidative stress, and determine whether the naringin (NG) co-administration can modify the effect of this compound on cognitive functions and inhibit any possible oxidative stress in the brain tissue of rats. Adult male Wistar rats were divided into six groups. Group I: control, Group II: BPA-treated rats (50 mg/kg/day), Group III, IV, V: BPA+NG (40, 80, 160 mg/kg/day), Group VI: NG (160 mg/kg/day) alone. Cognitive functions were evaluated using step-down latency (SDL) on a passive avoidance apparatus, and transfer latency (TL) in elevated plus-maze. A significant decrease in SDL, prolongation of TL, noticeable oxidative impairment and increase in acetylcholinesterase activity were observed in the BPA-treated in comparison with the control group. Also, the co-administration of NG (160 mg/kg) antagonized the effect of BPA on SDL and TL, attenuated oxidative damage by lowering malondialdehyde and nitrite concentrations and restored superoxide dismutase, catalase, and glutathione S-transferase activities. On the other hand, acetylcholinesterase activity was reduced in the groups co-administred with NG (80 or 160 mg/kg) and BPA in comparison with the BPA alone-treated group. The present study highlighted the therapeutic potential of NG against BPA-induced cognitive impairment and oxidative damage.

The capacity of human umbilical cord mesenchymal stem cells (hUMSCs)  for migration and homing is very important in regenerative medicine. A detoxified derivative of lipopolysaccharides (LPS) that lacks many of the endotoxic properties of LPS is monophosphoryl lipid A (MPLA).  Effects of MPLA on the induction of MSCs migration, have not yet been studied. Also, studies have shown that supernatant of Lactobacillus acidophilus (SLA) culture medium, can stimulate the proliferation of macrophages and lymphocytes in vitro by affecting the properties of the chemotaxis and angiogenesis. Our present study aimed to understanding of the migration of hUMSCs during treatment with MPLA and LS, separately. HUMSCs were isolated from human umbilical cord and were characterized by investigating surface markers (CD105, CD90, anti-CD29, CD45, and CD34) and their differentiation into adipogenic and osteogenic lineages. HUMSCs were treated with MPLA (10-3 µg/ml) and SLA (3 µl/ml). The morphological changes were not observed in both treated MSCs. Expression levels of migration markers were determined by quantitative reverse transcription PCR analysis on 2, 4, 6 days after treatment. Results showed that VEGF and MMP-2 but not CXCR-4 was increased in the presence of both treatments. Also, SLA led to a decrease and increase of the expression of VLA-4 and VCAM-1, respectively, while MPLA increased both VLA-4 and VCAM-1 expression.Therefore, it can be suggested that MPLA has more prominent results than SLA, but both treatments can probably be considered as an inducing factor in migration.

Acne vulgaris (AV) is a common skin disease that causes physical and psychological problems for affected individual. In addition to systemic changes in hormone levels, overproduction of local steroids, especially androgens are associated with AV. Cytochrome (CYP) 19 is involved in the synthesis of estrogens. The aim of the present study was to investigate the influence of CYP19A.