Deletion in a regulatory region is associated with underexpression of miR-148b­3p in patients with prostate cancer.

Prostate cancer (PCa) is the leading cause of cancer-related death in men. This pathology is complex and heterogeneous; therefore, elucidating the molecular mechanisms that lead to its origin and progression is imperative. MicroRNAs (miRNAs or miRs) are part of the epigenetic machinery that regulates the expression of human genes, therefore, mutations in the genes that encode them can lead to a dysregulation in their expression, which directly impacts their target genes, which could be oncogenes or tumor suppressor genes. In PCa several dysregulated expression levels of miRNAs are associated with perturbed cellular processes. A differential expression of miRNAs such as miR-145-5p and miR-148-3p has been observed in PCa, possibly due to mutations in regions near the miRNAs. However, the molecular mechanisms that lead to the dysregulation of these miRNAs still need to be clarified. Therefore, the present study aimed to analyze the expression of miRNAs and their relationship with mutations in patients with and without PCa. In total, 71 patients were analyzed: 41 of whom had PCa (CAP group) and 30 with benign pathology (BPD group). Underexpression was observed in miR-145-5p and miR-148b-3p in PCa patients (P=0.03 and P=0.001, respectively). In miR-145-5p, no mutations related to its expression were identified. For miR-148b-3p, a set of mutations were identified in the chr12:54337042/54337043 region, which were grouped into the mutation named DelsAAG. Although this mutation's abnormal allele is related to PCa (P=0.017), a statistically significant difference was observed in the expression of miR-148b-3p between carriers and non-carriers of the mutated allele, identifying a mechanism likely to be involved in the miR-148b-3p dysregulation.

Expression Analysis of miRNAs and Their Potential Role as Biomarkers for Prostate Cancer Detection.

Prostate cancer (PCa) is the second most frequent cancer diagnosed in men worldwide. The detection methods for PCa are either unreliable, like prostate-specific antigen (PSA), or extremely invasive, such as in the case of biopsies. Therefore, there is an urgent necessity for reliable and less invasive detection procedures that can differentiate between patients with benign diseases and those with cancer. In this matter, microRNAs (miRNAs) are suggested as potential biomarkers for cancer. MiRNAs have been found to be dysregulated in several different cancers, and these genetic alterations may present specific signatures for a given malignancy. Here, we examined the expression of miR141-3p, miR145-5p, miR146a-5p, and miR148b-3p in human tissue samples of PCa (n = 41) and benign prostatic diseases (BPD) (n = 30) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We combined the expression results with patient clinicopathological characteristics in logistic regression models to create accurate PCa predictive models. A model including information of miR148b-3p and patient age showed relevant prediction results (area under the curve [AUC] = 0.818, precision = 0.763, specificity = 0.762, and accuracy = 0.762). A model including all four miRNAs and patient age presented outstanding prediction results (AUC = 0.918, precision = 0.861, specificity = 0.861, and accuracy = 0.857). Our results represent a potential novel procedure based on logistic regression models that utilize miRNA expressions and patient age to assist with PCa diagnosis.

Altered Expression of Survivin Variants S-2B and S-WT in Breast Cancer Is Related to Adipokine Expression.

Breast cancer (BCa) is one of the leading causes of death in women with these types of malignancies. Early detection is pivotal to improve prognosis and reduce mortality. Several proteins and genes have been proposed as biomarkers for cancer; however, further studies are required before a molecule is accepted as a definitive biomarker. This study was aimed at investigating the expression of survivin variants S-WT, S-2B, and S-ΔEx3, as well as adipokines LEP and ADIPOQ in breast cancer. Breast samples were obtained from patients with (n = 27) and without (n = 20) BCa, and relative gene expression was assessed by RT-qPCR. S-WT and S-2B showed a significant increase in BCa samples (p = 0.005 and p = 0.001, respectively) and in high-aggressiveness BCa (p = 0.026 and p = 0.037, respectively). Despite S-ΔEx3 expression remained globally unchanged, when dividing BCa samples according to the stage, this gene showed a significant tendency to increase towards more advanced stages, and the exact opposite effect was observed for LEP. Furthermore, LEP expression showed a negative correlation with S-2B (p = 0.005) and S-WT (p = 0.011), and in the same manner, ADIPOQ was negatively related with these two survivin variants (p = 0.001 and p = 0.005, respectively). Interestingly, S-ΔEx3 expression appears unaffected by LEP and ADIPOQ expressions. Our results highlight the importance of investigating specific variants of a given gene, as sequence variation may grant different correlation with other important structures and diseases.

Expression of miR-148b-3p is correlated with overexpression of biomarkers in prostate cancer.

Prostate cancer (PCa) is one of the leading causes of death among men. Genes such as PCA3, PSA, and Fra-1 are suggested to serve as potential tools for the detection of PCa, as they are deregulated during this pathology. A similar event occurs with small non-coding RNAs, called miRNAs, specifically miR-195-5p, miR-133a-3p, and miR-148b-3p, which were analyzed in a Chinese population and suggested to be possible candidates for PCa diagnosis. We evaluated the expression levels of three miRNAs and three genes in tissue samples of PCa and benign prostate disease, such as benign prostatic hyperplasia, or prostatitis, in order to determine their potential as candidates for PCa detection. Our results showed a statistically significant overexpression of 279-fold increase in PSA levels and a 1,012-fold increase in PCA3 levels in PCa patients compared to benign prostate disease patients (p = 0.001 and p = 0.002, respectively). We observed a positive correlation between the expression of miR-148b-3p and the expression of PSA and PCA3 genes, two established biomarkers in PCa. The expression of miR-148b-3p was not related to clinical characteristics, such as age and weight, as observed for the other miRNAs analyzed, suggesting its potential as a biomarker for detection of this pathology.