This study analyzed the effect of distinct F concentrations and exposure periods on the mitochondrial activity of complex I-III and II-III in the liver. Taken together, our findings suggest that OTUB1 is an unfavourable candidate for breast cancer diagnosis, but it could be a very promising molecular target for breast cancer therapeutic intervention.įluoride (F) can induce changes in the expression of several liver proteins, most of them localized in the mitochondria and its effect is dose- and time-dependent. Meanwhile, PPI network analysis revealed that OTUB1 is the immediate neighbour for 31 cancer proteins and DEGs ESR1 and BIRC3, a strategic topological position for perturbing cancer interactome. Despite a significant difference in some microarray probes and qPCR experiment, the fold change value is too small to ensure sensitivity in breast cancer diagnosis. This result is consistent with qPCR analysis, with qPCR showing a larger log(FC) value of 2.44-4.95. Microarray datasets analysis showed that OTUB1 expression value is significantly higher in MCF-7 in seven out of 16 probes with log(FC) value ranging from 0.24 to 1.43. Protein-protein interaction (PPI) network was constructed using Cytoscape ver3.6.0 to analyse the topological position of OTUB1 in cancer and differentially expressed genes (DEGs) neighbourhoods. Relative expression of OTUB1 in MCF-7 and MCF-10A was compared using bioinformatics analysis on microarray datasets obtained from Gene Expression Omnibus and validated by qPCR experiment. Prompted by the lack of information about OTUB1’s potential as a breast cancer molecular marker, this study is conducted to evaluate the significance of OTUB1 as a diagnostic tool based on its expression in MCF-7, as well as to validate its potential as a therapeutic target using network-based analysis. OTUB1 is a deubiquitin enzyme that plays important role in cancer-related events. In addition, fluorosis-susceptible mice have plasma glucose levels higher than fluorosis-resistant mice on exposure to F, and this is not affected by exercise. In conclusion, the findings suggest an increased state of oxidative stress in fluorosis-susceptible mice that might be exacerbated by the treatment with F. The results also showed a decrease in muscle protein expression in Group I S-mice compared with their R-mice counterparts. There was an increase in liver proteins involved in energy flux and antioxidant enzymes in non-exercise groups (I, II) of S-mice in comparison with the corresponding groups of R-mice. In S-mice, the mean plasma glucose level was significantly higher in Group II compared with Groups I and III. In R-mice, exercise resulted in an increase in F accumulation in the femur. Overall, mean F concentrations in the plasma and femur were significantly higher in R-mice compared with S-mice. Ninety male mice (45 R-mice and 45 S-mice) were randomized into three groups: (SI RI) No-F, No-Exercise, (SII RII) 50 ppm F, No-Exercise, (SIII RIII) 50 ppm F, Exercise. We compared the parameters related to glucose homeostasis, and liver and muscle proteomes in fluorosis-susceptible (A/J S) and fluorosis-resistant (129P3/J R) mice in response to fluoride (F) exposure and exercise.
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