Downregulation of Drosha, Dicer, and DGCR8 mRNAs in Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis

Akhlaghi, Maassoumeh; Soltani, Shahin; Jamshidi, Fatemeh; Faezi, Seyedeh Tahereh; Aslani, Saeed; Poursani, Shiva; Jamshidi, Ahmadreza; Mahmoudi, Mahdi

doi:10.22631/rr.2018.69997.1055

Cited by 2 publications

(2 citation statements)

References 39 publications

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“…Dicer mRNA expression has been found to be significantly reduced in fibroblast-like synoviocytes (FLSs) of patients but not in isolated peripheral blood mononuclear cells (PBMCs) [130], a fact that indicates that differential Dicer expression in patients is located in specific cells (Figure 6). The latter observations are supported by a study on another group of RA patients that also revealed no statistically significant Dicer expression difference in PBMCs when compared to that of healthy individuals [131]. Thus, Dicer might contribute to the pathogenesis by controlling the differential expression of several miRNAs in RA patients, leading to the regulation of immune response, cell cycle and apoptosis [132,133].…”

Section: Rheumatoid Arthritismentioning

confidence: 78%

Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies

Theotoki

Pantazopoulou

Georgiou

et al. 2020

IJMS

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Gene expression dictates fundamental cellular processes and its de-regulation leads to pathological conditions. A key contributor to the fine-tuning of gene expression is Dicer, an RNA-binding protein (RBPs) that forms complexes and affects transcription by acting at the post-transcriptional level via the targeting of mRNAs by Dicer-produced small non-coding RNAs. This review aims to present the contribution of Dicer protein in a wide spectrum of human pathological conditions, including cancer, neurological, autoimmune, reproductive and cardiovascular diseases, as well as viral infections. Germline mutations of Dicer have been linked to Dicer1 syndrome, a rare genetic disorder that predisposes to the development of both benign and malignant tumors, but the exact correlation of Dicer protein expression within the different cancer types is unclear, and there are contradictions in the data. Downregulation of Dicer is related to Geographic atrophy (GA), a severe eye-disease that is a leading cause of blindness in industrialized countries, as well as to psychiatric and neurological diseases such as depression and Parkinson’s disease, respectively. Both loss and upregulation of Dicer protein expression is implicated in severe autoimmune disorders, including psoriasis, ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis and autoimmune thyroid diseases. Loss of Dicer contributes to cardiovascular diseases and causes defective germ cell differentiation and reproductive system abnormalities in both sexes. Dicer can also act as a strong antiviral with a crucial role in RNA-based antiviral immunity. In conclusion, Dicer is an essential enzyme for the maintenance of physiology due to its pivotal role in several cellular processes, and its loss or aberrant expression contributes to the development of severe human diseases. Further exploitation is required for the development of novel, more effective Dicer-based diagnostic and therapeutic strategies, with the goal of new clinical benefits and better quality of life for patients.

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Section: Rheumatoid Arthritismentioning

confidence: 78%

Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies

Theotoki

Pantazopoulou

Georgiou

et al. 2020

IJMS

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“…Environmental and genetic factors both could play roles in protein citrullination, which results in forming new antigens and may be correlated with breakdown of tolerance . Immune cells including T helper (Th)1, Th17, B cells, dendritic cells (DCs), synovial fibroblasts (SFs), and osteoclasts play roles in RA pathogenesis …”

Section: Introductionmentioning

confidence: 99%

microRNA involvement in the regulation of survivin in peripheral blood mononuclear cells from rheumatoid arthritis patients

et al. 2019

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Aim Impaired regulation of immune tolerance results in autoimmune diseases, such as rheumatoid arthritis (RA). Survivin is an anti‐apoptotic protein and can induce cellular mitosis. In the current study, we assessed the transcript level of total survivin (survivin‐TS) and its three major variants and evaluated the expression level of important micro RNAs (miRNAs) involved in survivin expression regulation in RA patients. Method Peripheral blood mononuclear cells (PBMCs) were isolated from 50 healthy controls and 50 RA‐active patients. RNA extraction was performed and then single‐strand complementary DNA was synthesized. Quantitative real‐time polymerase chain reaction was used to assess the expression level of survivin‐TS and its variants with effective miRNAs in PBMCs. Results Overexpression of survivin‐2B (fold change = 1.57, P = 0.005), survivn‐ΔEx3 (fold change = 1.93, P = 0.009) and downregulation of survivin‐WT (fold change = 0.64, P = 0.0002) were found in PBMCs of patients, while messenger RNA (mRNA) expression of survivin‐TS had no significant difference between RA patients and controls. Expression levels of miR‐335‐5p, miR‐485‐5p, miR‐16‐5p, miR‐150‐5p, miR‐34a‐5p, and miR‐203a‐3p were significantly increased in PBMCs from patients compared with healthy controls. In a correlation study, dysregulation of these miRNAs were not correlated with mRNA expression level of survivin. Conclusion While survivin‐TS was not differently expressed in RA patients, its variants had altered expression. Although miRNAs were aberrantly expressed in PBMCs from RA subjects, they did not regulate survivin‐TS. miRNAs might be involved in RA pathogenesis, but not through controlling survivin.

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Downregulation of Drosha, Dicer, and DGCR8 mRNAs in Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis

Cited by 2 publications

References 39 publications

Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies

Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies

microRNA involvement in the regulation of survivin in peripheral blood mononuclear cells from rheumatoid arthritis patients

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