Application of RNA interference in treating human diseases

Angaji, S Abdolhamid; Hedayati, Sara Sadate; Poor, Reihane Hosein; Madani, Safoura; Poor, Sanaz Samad; Panahi, Samin

doi:10.1007/s12041-010-0073-3

Cited by 45 publications

(13 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over 700 miRNAs have been identified in the human genome, of which 20% to 30% regulate human protein coding genes [2]. A total number of 8291 predicted miRNA target genes were related to these 86 miRNAs.…”

Section: Discussionmentioning

confidence: 99%

“…MiRNA regulates approximately 30% of the encoding genes of the human genome at the posttranscriptional level by incorporating into the RNA induced silencing complex (RISC) and preferentially binding to the 3’ untranslated region (3’UTR) of target mRNA. RISC then inhibits gene expression either by mRNA degradation or inhibiting translation [2]. Among thousands of target genes that are regulated by miRNA [3], many belong to biological pathways including immune response and apoptosis [4].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Circulating microRNA: a novel potential biomarker for early diagnosis of Intracranial Aneurysm Rupture a case control study

Jin

et al. 2013

J Transl Med

View full text Add to dashboard Cite

ObjectiveTo investigate warning effect of serum miRNA for intracranial aneurysm rupture through microarray hybridization.Methods24 were selected from 560 patients in our department and divided into group A, B, C and D. They are aneurysms with daughter aneurysms group, aneurysm without daughter aneurysms group, ruptured aneurysms group and angiography negative group. Then a microarray study was carried out using serum miRNA. Differentially expressed miRNAs were identified. Cluster analysis was performed in order to make the results looks more intuitive and potential gene targets were retrieved from miRNA target prediction databases.ResultsMicroarray study identified 86 miRNAs with significantly different (p < 0.05) expression levels between three experimental groups and control group. Among them 69 are up-regulated and 17 are down-regulated. All miRNAs in group A are up-regulated, while there are up and down-regulated in group B and C. A total of 8291 predicted target genes are related to these miRNAs. Bioinformatic analysis revealed that several target genes are involved in apoptosis and activation of cells associated with function of vascular wall.ConclusionOur gene level approach reveals several different serum miRNAs between normal people and aneurysm patients, as well as among different phases of aneurysm, suggesting that miRNA may participate in the regulation of the occurrence and development of intracranial aneurysm, and also have warning effect for intracranial aneurysm rupture. All differently expressed miRNA in group A are up-regulated, which may suggesting protective function of miRNA for intracranial vascular wall.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating microRNA: a novel potential biomarker for early diagnosis of Intracranial Aneurysm Rupture a case control study

Jin

et al. 2013

J Transl Med

View full text Add to dashboard Cite

show abstract

“…miRNAs are a class of small non-coding RNAs that bind preferentially to the 3′-untranslated region (3′-UTR) of target mRNA sequences and transport them to the RNA-induced silencing complex, which results in the downregulation of gene expression by mRNA degradation and inhibition of translation (18). This process contributes to the regulation of crucial biological activities, including cell proliferation, apoptosis and differentiation (19,20).…”

Section: Introductionmentioning

confidence: 99%

miRNA-504 inhibits p53-dependent vascular smooth muscle cell apoptosis and may prevent aneurysm formation

Cao

Cai

Liu

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

Abdominal aortic aneurysm (AAA) is a common disease that is associated with the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). VSMCs are regulated by microRNAs (miRNA). The aim of the present study was to identify miRNA sequences that regulate aortic SMCs during AAA. miRNA-504 was identified using a miRNA PCR array and by reverse transcription-quantitative polymerase chain reaction analysis, and its expression levels were observed to be downregulated in the aortic cells derived from patients with AAA when compared with controls. Transfection of SMCs with pMSCV-miRNA-504 vector was performed, and cell proliferation and the expression levels of proliferating cell nuclear antigen (PCNA), replication factor C subunit 4 (RFC4), B-cell lymphoma-2 (Bcl-2) and caspase-3/9 were measured by western blotting. The mechanisms underlying the effects of miRNA-504 was then analyzed. The results demonstrated that overexpression of miRNA-504 significantly upregulated the expression levels of PCNA, RFC4 and Bcl-2, while caspase-3/9 expression was significantly inhibited when compared with non-targeting controls. In addition, miRNA-504 overexpression was observed to promote the proliferation of SMCs. The expression level of the tumor suppressor, p53, which is known to be a direct target of miRNA-504, was inhibited following transfection of SMCs with pMSCV-miRNA-504. In addition, the expression of the downstream targets of p53, p21 and Bcl-like protein-4, were significantly reduced following overexpression of miRNA-504. These results revealed the anti-apoptotic role of miRNA-504 in SMCs derived from patients with AAA via direct targeting of p53.

show abstract

“…About 30% of the encoding genes in the human genome are regulated by miRNA in a posttranscriptional manner, which bind to the target mRNAs’ 3′untranslated region (3′UTR) preferentially and incorporate into the RNA-induced silencing complex (RISC). Then, RISC suppress expression of genes either by inhibiting translation or inducing degradation of mRNAs [5]. Among the numerous miRNA-regulated target genes, many are involved in biological pathways, such as apoptosis and immune response [6].…”

Section: Introductionmentioning

confidence: 99%

Aberrant Expression of microRNA-9 Contributes to Development of Intracranial Aneurysm by Suppressing Proliferation and Reducing Contractility of Smooth Muscle Cells

et al. 2016

View full text Add to dashboard Cite

BackgroundMiR-9 is reportedly involved with many diseases, such as acute myeloid leukemia and liver oncogenesis. In the present study we investigated the molecular mechanism, including the potential regulator and signaling pathways, of MYOCD, which is the gene that in humans encodes the protein myocardin.Material/MethodsWe searched the online miRNA database (www.mirdb.org) with the “seed sequence” located within the 3′-UTR of the target gene, and then validated MYOCD to be the direct gene via luciferase reporter assay system, and further confirmed it in cultured cells by using Western blot analysis and realtime PCR.ResultsWe established the negative regulatory relationship between miR-9 and MYOCD via studying the relative luciferase activity. We also conducted realtime PCR and Western blot analysis to study the mRNA and protein expression level of MYOCD between different groups (intracranial aneurysm vs. normal control) or cells treated with scramble control, miR-9 mimics, MYOCD siRNA, and miR-9 inhibitors, indicating the negative regulatory relationship between miR-9 and MYOCD. We also investigated the relative viability of smooth muscle cells when transfected with scramble control, miR-9 mimics, MYOCD siRNA, and miR-9 inhibitors to validate that miR-9 t negatively interferes with the viability of smooth muscle cells. We then investigated the relative contractility of smooth muscle cells when transfected with scramble control, miR-9 mimics, MYOCD siRNA, and miR-9 inhibitors, and the results showed that miR-9 weakened contractility.ConclusionsOur findings show that dysregulation of miR-9 is responsible for the development of IA via targeting MYOCD. miR-9 and its direct target, MYOCD, might novel therapeutic targets in the treatment of IA.

show abstract

Application of RNA interference in treating human diseases

Cited by 45 publications

References 114 publications

Circulating microRNA: a novel potential biomarker for early diagnosis of Intracranial Aneurysm Rupture a case control study

Circulating microRNA: a novel potential biomarker for early diagnosis of Intracranial Aneurysm Rupture a case control study

miRNA-504 inhibits p53-dependent vascular smooth muscle cell apoptosis and may prevent aneurysm formation

Aberrant Expression of microRNA-9 Contributes to Development of Intracranial Aneurysm by Suppressing Proliferation and Reducing Contractility of Smooth Muscle Cells

Contact Info

Product

Resources

About