Effects of Aerobic Exercise Training on MyomiRs Expression in Cachectic and Non-Cachectic Cancer Mice

We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers’ cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.

MicroRNA Expression Profiling in Porcine Liver, Jejunum and Serum upon Dietary DON Exposure Reveals Candidate Toxicity Biomarkers

Deoxynivalenol (DON), a frequent mycotoxin worldwide, impairs human and animal health. The response of microRNAs, small non-coding RNAs, to DON has been scarcely investigated, but holds remarkable potential for biomarker applications. Hence, we aimed to investigate DON-induced changes in the microRNA expression in porcine liver, jejunum and serum by combining targeted and untargeted analyses. Piglets received uncontaminated feed or feed containing 900 µg/kg and 2500 µg/kg DON for four weeks, followed by a wash-out period. In tissue, only slight changes in microRNA expression were detected, with ssc-miR-10b being downregulated in liver of DON-exposed piglets. In serum, several microRNAs were differentially expressed upon DON exposure, four of which were validated by qPCR (ssc-miR-16, ssc-miR-128, ssc-miR-451, ssc-miR-205). The serum microRNA response to DON increased over time and declined after removal of contaminated diets. Receiver operating curve analyses for individual microRNAs were significant, and a combination of the four microRNAs increased the predictive capacity for DON exposure. Predicted microRNA target genes showed enrichment of several pathways including PIK3-AKT, Wnt/β-catenin, and adherens junctions. This study gives, for the first time, a comprehensive view of the porcine microRNA response to DON, providing a basis for future research on microRNAs as biomarkers for mycotoxins.

Serum miR-373-3p and miR-194-5p Are Associated with Early Tumor Progression during FOLFIRINOX Treatment in Pancreatic Cancer Patients: A Prospective Multicenter Study

In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease stages were included in this study, of whom 25% showed progressive disease during FOLFIRINOX according to the RECIST criteria. MiRNA expression was analyzed in serum collected before the start and after one cycle of chemotherapy. In the discovery cohort (n = 12), a 352-miRNA RT-qPCR panel was used. In the validation cohorts (total n = 120), miRNA expression was detected using individual RT-qPCR miRNA primers. Before the start of FOLFIRINOX, serum miR-373-3p expression was higher in patients with progressive disease compared to patients with disease control after FOLFIRINOX (Log2 fold difference (FD) 0.88, p = 0.006). MiR-194-5p expression after one cycle of FOLFIRINOX was lower in patients with progressive disease (Log2 FD −0.29, p = 0.044). Both miRNAs were predictors of early tumor progression in a multivariable model including disease stage and baseline CA19-9 level (miR-373-3p odds ratio (OR) 3.99, 95% CI 1.10–14.49; miR-194-5p OR 0.91, 95% CI 0.83–0.99). MiR-373-3p and miR-194-5p did not show an association with OS after adjustment for disease stage, baseline CA19-9, and chemotherapy response. In conclusion, high serum miR-373-3p before the start and low serum miR-194-5p after one cycle are associated with early tumor progression during FOLFIRINOX.

The Role of Serum microRNA (hsa-miR-519d) And the Associated Target Gene (SQSTM1) As Diagnostic Biological Molecular Biomarkers for Hepatocellular Carcinoma

Background Hepatocellular carcinoma (HCC) is the most common primary liver cancer. The mortality of liver cancer worldwide is ranked as fourth between other cancer causes in males and females. In Egypt, it is a major problem due to the high prevalence of Hepatitis C Virus infection. Objective To characterize the expression of new serum non-coding RNA microRNA (hsa-miR519d) and the associated target gene (SQSTM1) to evaluate their usefulness as diagnostic molecular biomarkers for HCC. Patients and Methods we assessed the expression of the microRNA (hsa-miR-519d-3p) and the mRNA of (SQSTM1) gene in serum samples from 50 participants: (34) HCC patients, (11) chronic liver infection patients and (5) normal volunteers, using Quantitative Real Time Polymerase Chain Reaction (qPCR). Results The results of both microRNA (miR-519d-3p) and mRNA of (SQSTM1) gene showed a significant upregulation of their serum level in the HCC group in comparison to chronic liver infection group. In addition, the results of the serum microRNA (miR-519d) and the messenger RNA of (SQSTM1) gene using receiver operating characteristic (ROC) curve showed higher sensitivity and specificity than that of AFP, as it was (91.2%-81.8%), (97.1%-100%) and (76.5%72.7%) respectively. Conclusion The serum microRNA (hsa-mir-519d-3p) and the serum mRNA of its targeted gene (SQSTM1) are both significantly upregulated in the serum of Hepatocellular carcinoma (HCC) patients. And that the (hsa-mir-519d-3p) stimulates the gene (SQSTM1) at the transcriptional level. Finally, we could conclude that the serum microRNA (hsa-mir-519d-3p) and the serum mRNA of (SQSTM1) gene can be used as diagnostic biomarkers for HCC with good sensitivity and specificity even for early stages of HCC in comparison with AFP.

Serum miR-148a And miR-152 Expression As Novel Noninvasive Biomarkers For Diagnosis And Prognostic Prediction of Multiple Myeloma

Objective: Multiple myeloma (MM) as a hematological malignancy remains mostly incurable at present. The aim of the current study was to investigate the potential of serum microRNA (miRNA) as a novel biomarker for MM.Methods: This study recruited 90 MM patients and 30 healthy controls. Bone marrow samples were obtained from 12 MM patients and 6 healthy controls. The expression level of miR-148a/152 was determined by qRT-PCR. The diagnostic performance and prognostic prediction of miR-148a/152 expression were analyzed by ROC curve and Kaplan-Meier method respectively. Serum IgA, IgG, κ light chain, λ light chain and β2 microglobulin levels were detected by immunoturbidimetry. Serum LDH level was detected by lactic acid substrate method.Results: The expression levels of miR-148a and miR-152 were elevated in serum and CD138+ plasma cells of MM patients as compared with controls (P<0.05). There was a statistically significant correlation between serum miR-148a/152 expression and the clinicopathological parameters of MM patients. Conclusion: The results of the present study suggest that circulating miR-148a and miR-152 may prove to be a marker for diagnosis and prognostic prediction of MM.