Altered microRNA (miRNA) expression is a common feature of Huntington’s disease (HD) and could participate in disease onset and progression. However, little is known about the underlying causes of miRNA disruption in HD. We and others have previously shown that mutant Huntingtin binds to Ago2, a central component of miRNA biogenesis, and disrupts mature miRNA levels. In this study, we sought to determine if miRNA maturation per se was compromised in HD. Towards this end, we characterized major miRNA biogenesis pathway components and miRNA maturation products (pri-miRNA, pre-miRNA, and mature) in human HD (N = 41, Vonsattel grades HD2-4) and healthy control (N = 25) subjects. Notably, the striatum (putamen) and cortex (BA39) from the same individuals were analyzed in parallel. We show that Ago2, Drosha, and Dicer were strongly downregulated in human HD at the early stages of the disease. Using a panel of HD-related miRNAs (miR-10b, miR-196b, miR-132, miR-212, miR-127, miR-128), we uncovered various types of maturation defects in the HD brain, the most prominent occurring at the pre-miRNA to mature miRNA maturation step. Consistent with earlier findings, we provide evidence that alterations in autophagy could participate in miRNA maturation defects. Notably, most changes occurred in the striatum, which is more prone to HTT aggregation and neurodegeneration. Likewise, we observed no significant alterations in miRNA biogenesis in human HD cortex and blood, strengthening tissue-specific effects. Overall, these data provide important clues into the underlying mechanisms behind miRNA alterations in HD-susceptible tissues. Further investigations are now required to understand the biological, diagnostic, and therapeutic implications of miRNA/RNAi biogenesis defects in HD and related neurodegenerative disorders.

No abstract

Background: MicroRNAs (miRNAs) have crucial roles in cellular and molecular processes related to different malignancies including chronic lymphocytic leukemia (CLL). Studies revealed altered miR-95 expression in several diseases. Long noncoding RNAs (lncRNAs) are a heterogeneous group of non-coding and regulatory RNAs. The present study was conducted to investigate the association of miR-95 expression with CLL by quantitative real-time PCR. Materials and Methods: Sixty samples, including 30 CLL and 30 healthy controls, were sampled during a period of 4 months. The expression of miR-95 was evaluated by quantitative real-time PCR in peripheral blood mononuclear cells from patients with CLL and in healthy subjects. Additionally, in silico pathway enrichment analysis was performed on validated and predicted targets of miR-95 in several databases, including miRecords and miRTarBase, while the interactions between predicted putative lncRNAs and genes and miRNA expression were examined with miRWalk. Results: The expression of miR-95 was found to be significantly reduced in patients with CLL compared to that in healthy controls (P < 0.005). Conclusion: miR-95 showed potential as a biomarker for the early diagnosis of patients with CLL. LncRNAs play a significant role in regulating cellular evolution, differentiation, and other processes and may be important regulators in tumorigenesis.

.

Background and Aims: Chronic lymphocytic leukemia (CLL) is the most common adult human leukemia. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Research has shown that in CLL, microRNAs can have function as oncogenes or tumor suppressors. Some studies demonstrated that the expression of microRNA-93 (miR-93) and microRNA-330 (miR-330) have been changed in several cancers, including lung, prostate, and colon cancer. We aimed to elucidate the changes in miR-93 and miR-330 expression in CLL patients in comparison with controls. Materials and Methods: In this case-control study, the expression levels of miR-93 and miR-330 was evaluated in 30 CLL patients who had referred to Omid Hospital, Isfahan, Iran, and 30 controls in peripheral blood mononuclear cells using reverse transcription quantitative PCR (RT-qPCR). Results: The expression of miR-93 and miR-330 were found to significantly increase in CLL patients compared with controls (p<0.0001). Conclusions: The findings indicated that miR-93 and miR-330 are probably the novel potential biomarker for early diagnosis of CLL, at least in Iranian patients. However, for a decisive result, further investigations are warranted

Background: Multiple sclerosis (MS) is an autoimmune disease that causes chronic inflammation of the central nervous system. MicroRNAs (miRNAs) are small non-coding RNAs 19-24 nucleotides long, which are differentially expressed in different tissues. The role of miRNAs in MS remains unclear. We assessed miR-10a transcript levels in MS patients during recurrence and two months after relapse. Materials and Methods:In this case-control study, we used real-time PCR to examine miR-10a expression in the peripheral blood mononuclear cells of 60 patients with relapsing-remitting multiple sclerosis (RRMS), 30 during recurrence and 30 two months after relapse, and 30 healthy subjects who were referred to the MS Clinic of Kashani Hospital, Isfahan Province. In silico analysis was also performed on the validated miR-10a targets using miRTarBase. Results: miR-10a expression was higher in RRMS patients during recurrence and two months after relapse (p < 0.0001 and p < 0.0001, respectively) than in the healthy subjects. Furthermore, in silico molecular signaling enrichment analysis identified 12 mRNAs as validated miR-10a targets. Conclusion: The expression of miR-10a was elevated in patients with RRMS compared to healthy subjects, suggesting that miR-10a could be a potential biomarker for RRMS diagnosis.

Background: Chronic lymphocytic leukemia (CLL) is the most common adult human leukemia. Studies revealed that microRNAs (miRNAs) can function as oncogenes or tumor suppressors in CLL and that the expression of miRNAs, such as miR-193b-3p and miR-376a-3p change in several diseases. We aimed to elucidate the changes in miR- 193b-3p and miR-376a-3p expression in CLL and determine their potential as diagnostic biomarkers for this disease. Materials and Methods: We investigated miR-193b-3p and miR-376a-3p expression by quantitative real-time PCR in peripheral blood mononuclear cells of 30 patients with CLL and 30 healthy individuals. Moreover, in silico molecular enrichment analysis was conducted on predicted and validated targets of miR-193b-3p and miR-376a-3p from the miRecords and miRTarBase databases. Results: The expression of miR-193b-3p and miR-376a-3p was significantly different between the two groups (P<0.0001 and P < 0.0001, respectively). Conclusion: Based on these findings, miR-193b-3p and miR-376a-3p could be novel biomarkers for the early diagnosis of CLL and could be used to design new CLL control strategies.

Altered microRNA (miRNA) expression is a common feature of Huntington's disease (HD) and could participate in disease onset and progression. However, little is known about the underlying causes of miRNA disruption in HD. We and others have previously shown that mutant Huntingtin (mHTT) binds to Ago2, a central component of miRNA biogenesis, and disrupts mature miRNA levels. In this study, we sought to determine if miRNA maturation per se was compromised in HD. Towards this end, we characterized t major miRNA biogenesis pathway components and miRNA maturation products (pri-miRNA, pre-miRNA, and mature) in human HD (N=41, Vonsattel grades HD2-4) and healthy control (N=25) subjects. Notably, the striatum (putamen) and cortex (BA39) from the same individuals were analyzed in parallel. We show that Ago2, Drosha, and Dicer were strongly downregulated in human HD at early stages of disease. Using a panel of HD-related miRNAs (miR-10b, miR-196b, miR-132, miR-212, miR-127, miR-128), we uncovered various types of maturation defects in HD brain, the most prominent occurring at the pre-miRNA to mature miRNA maturation step. Consistent with earlier findings, we provide evidence that alterations in autophagy could participate in miRNA maturation defects. Notably, most changes occurred in the striatum, which is more prone to HTT aggregation and neurodegeneration. Likewise, we observed no significant alterations in miRNA biogenesis in human HD cortex and blood, strengthening tissue-specific effects. Overall, these data provide important clues into the underlying mechanisms behind miRNA alterations in HD-susceptible tissues. Further investigations are now required to understand the biological, diagnostic, and therapeutic implications of miRNA/RNAi biogenesis defects in HD and related neurodegenerative disorders.