Functional roles of miR-625-5p and miR-874-3p in the progression of castration resistant prostate cancer.

AIMS: Androgen receptor (AR) signaling is important in normal prostate and prostate tumor tissues. Thus, the new therapeutic strategies targeting ARs may also be important for treatment of prostate cancer (PC) and its biology. The studies have shown that miRNAs to be dysregulated in PC progression. Therefore, in the present study, differentially expressed miRNAs that predictively target the ARs were identified and investigated by in silico analysis. MAIN METHODS: Cellular proliferation, qPCR, western blot and apoptosis assays were performed to investigate the molecular mechanism of the selected miRNAs in the PC cells. KEY FINDINGS: In our miRNA qPCR study, several miRNAs were found to be differentially regulated in castration resistant prostate cancer (CRPC) cells (LNCaP-Abl and LNCaP-104R2) compared with androgen dependent (AD) cells (LNCaP). The expression levels of miR-625-5p and miR-874-3p were significantly increased in LNCaP-Abl (2.62-fold, p = 0.0002; 4.00-fold, p = 0.00002, respectively) and LNCaP-104R2 (2.44-fold, p = 0.0455; 3.77-fold, p = 0.0383, respectively) compared with AD cells. The expression levels of AR and prostate specific antigen were increased in PC cells compared with AD cells. Furthermore, transfection of PC cells with anti-miRs suppressed their proliferation and AR protein levels (p < 0.05). SIGNIFICANCE: Several differentially regulated miRNAs were identified in CRPC cells, including miR-625-5p and miR-874-3p that are potentially involved in PC progression. These results may provide novel insights into the molecular mechanism underlying CRPC cells and miRNA applications may constitute a new and alternative method to prevent development of CRPC cells in the future.

Effects of the dopamine transporter gene on neuroimaging findings in different attention deficit hyperactivity disorder presentations.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a phenotipically and neurobiologically heterogeneous disorder. Deficiencies at different levels in response inhibition, differences in dopamine transporter genotype (DAT1) and various symptomatic presentations contribute to ADHD heterogeneity. Integrating these three aspects into a functional neuroimaging research could help unreval specific neurobiological components of more phenotipically homogeneous groups of patients with ADHD. During the Go-NoGo trial, we investigated the effect of the DAT1 gene using 3 T MRI in 72 ADHD cases and 24 (TD) controls that typically developed between the ages 8 and 15 years. In the total ADHD group, DAT1 predicted homozygosity for the 10R allele and hypoactivation in the anterior cingulate cortex and paracingulate cortex. There were no significant activation differences between DAT1 10R/10R homozygotes and 9R carriers in TD controls. Subjects with predominantly inattentive ADHD (ADHD-I) presentation with DAT1 10R/10R homozygous reduced neuronal activation during Go trial particularly in the frontal regions and insular cortex, and in the parietal regions during NoGo trial (brain regions reported as part of Default Mode Network- DMN). Additionally, DAT1 10R/10R homozygousness was associated with increased occipital zone activation during only the Go trial in the ADHD combined presentation (ADHD-C) group. Our results point the three main findings: 1) The DAT1 gene is 10R homozygous for differentiated brain activation in ADHD cases but not in the TD controls, supporting the DAT1 gene as a potential marker for ADHD, 2) The relationship between the DAT1 gene and the occipital regions in ADHD-C group which may reflect compensatory mechanisms, 3) The relationship between DAT1 gene and the reduced DMN suppression for 9R carriers probabaly stems from the ADHD-I group.

DRD4 genotyping may differentiate symptoms of attention-deficit/hyperactivity disorder and sluggish cognitive tempo

Objective: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3′-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). Methods: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. Results: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. Conclusion: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.

DRD4 genotyping may differentiate symptoms of attention-deficit/hyperactivity disorder and sluggish cognitive tempo.

OBJECTIVE: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3'-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). METHODS: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. RESULTS: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. CONCLUSION: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.