Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Faculty of Health Science and Medicine, Bond University, Robina, Queensland, Australia. Electronic address: .
Journal of Affective Disorders (Impact Factor: 3.38). 05/2012; 141(2-3):261-9. DOI: 10.1016/j.jad.2012.03.037
Source: PubMed


Immune dysfunction associated with a disease often has a molecular basis. A novel group of molecules known as microRNAs (miRNAs) have been associated with suppression of translational processes involved in cellular development and proliferation, protein secretion, apoptosis, immune function and inflammatory processes. MicroRNAs may be implicated in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), where immune function is impaired. The objective of this study was to determine the association between miRNAs in cytotoxic cells and CFS/ME.
Natural Killer (NK) and CD8(+)T cells were preferentially isolated from peripheral blood mononuclear cells from all participants (CFS/ME, n=28; mean age=41.8±9.6years and controls, n=28; mean age=45.3±11.7years), via negative cell enrichment. Following total RNA extraction and subsequent synthesis of cDNA, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of nineteen miRNAs.
There was a significant reduction in the expression levels of miR-21, in both the NK and CD8(+)T cells in the CFS/ME sufferers. Additionally, the expression of miR-17-5p, miR-10a, miR-103, miR-152, miR-146a, miR-106, miR-223 and miR-191 was significantly decreased in NK cells of CFS/ME patients in comparison to the non-fatigued controls.
The results from these investigations are not yet transferable into the clinical setting, further validatory studies are now required.
Collectively these miRNAs have been associated with apoptosis, cell cycle, development and immune function. Changes in miRNAs in cytotoxic cells may reduce the functional capacity of these cells and disrupt effective cytotoxic activity along with other immune functions in CFS/ME patients.

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    • "In cancer-associated fibroblasts, Aprelikova et al. showed that miR-148a was downregulated compared with matched normal tissue fibroblasts established from patients with endometrial cancer and wingless-type MMTV integration site family, member 10B (WNT10B) was a direct target of miR-148a [42]. In some nontumor diseases, such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), miR-152 was significantly decreased in NK cells of CFS/ME patients compared with nonfatigued controls [25]. "
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    ABSTRACT: MicroRNAs(miRNA) are noncoding RNAs of about 19--23 nucleotides that are crucial for many biological processes. Members of the microRNA-148/152(miR-148/152) family, which include microRNA-148a(miR-148a), microRNA-148b(miR-148b), and microRNA-152(miR-152), are expressed differently in tumor and nontumor tissues and are involved in the genesis and development of disease. Furthermore, members of the miR-148/152 family are important in the growth and development of normal tissues. Members of the miR-148/152 family regulate target genes and are regulated by methylation of CPG islands. In this review, we report recent studies on the expression of members of the miR-148/152 family, methylation of CPG islands, and their target genes in different diseases, as well as in normal tissues.
    Molecular Cancer 05/2013; 12(1):43. DOI:10.1186/1476-4598-12-43 · 4.26 Impact Factor
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    • "Data for the role for NK cell-intrinsic miRNA in these diseases is limited, but an important area of active investigation. For example , it was recently found that in patients with chronic fatigue syndrome, certain highly expressed NK miRNAs, such as miR- 21, were significantly decreased in NK cells (Brenu et al., 2012). Most of the existing literature regarding the role of NK miRNAs in disease focuses on NK cell malignancies. "
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    ABSTRACT: Natural killer (NK) cells are innate immune lymphocytes critical for host defense against viral infection and surveillance against malignant transformation. MicroRNAs (miRNAs) are a family of small, non-coding RNAs that regulate a wide variety of cellular processes. Recent advances have highlighted the importance of miRNA-mediated post-transcriptional regulation in NK cell development, maturation, and function. This review focuses on several facets of this regulatory mechanism in NK cells: (1) the expressed NK cell miRNA transcriptome; (2) the impact of total miRNA deficiency on NK cells; (3) the role of specific miRNAs regulating NK cell development, survival, and maturation; (4) the intrinsic role of miRNAs regulating NK cell function, including cytokine production, proliferation, and cytotoxicity; and (5) the role of NK cell miRNAs in disease. Currently our knowledge of how miRNAs regulate NK cell biology is limited, and thus we also explore key open questions in the field, as well as approaches and techniques to ascertain the role of individual miRNAs as important molecular regulators.
    Frontiers in Immunology 02/2013; 4:44. DOI:10.3389/fimmu.2013.00044
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    ABSTRACT: Background: MicroRNAs (miRNAs) are present in body fluids and may have the potential to serve as disease biomarkers. This study explored the clinical value of miRNAs in serum and urine as biomarkers for idiopathic childhood nephrotic syndrome (NS). Methods: We obtained serum samples from 159 NS children (24 steroid resistant and 135 steroid sensitive), 109 age/sex-matched healthy controls and 44 children with other kidney diseases. Serum miRNAs were analyzed with the TaqMan Low Density Array and then validated with a quantitative reverse-transcription PCR assay with 126 individual samples. Moreover, we collected paired serum samples from 50 patients before and after treatment to determine the value of these miRNAs for condition assessment. In addition, urine samples from these patients were examined for candidate miRNAs. Results: The concentrations of serum miR-30a-5p, miR-151-3p, miR-150, miR-191, and miR-19b were highly increased in NS children compared with controls (P < 0.0001). The urinary miR-30a-5p concentration was also increased in NS (P = 0.001). The area under the ROC curve and the odds ratio for the combined 5 serum miRNAs were 0.90 (95% CI, 0.86-0.94; P < 0.0001) and 40.7 (95% CI, 6.06-103; P < 0.0001), respectively. Moreover, the concentrations of the 5 serum miRNAs and urinary miR-30a-5p markedly declined with the clinical improvement of the patients. Conclusions: We determined that 5 distinct serum miRNAs and urinary miR-30a-5p were increased in NS children. These circulating or urinary miRNAs may represent potential diagnostic and prognostic biomarkers for idiopathic pediatric NS.
    Clinical Chemistry 01/2013; 59(4). DOI:10.1373/clinchem.2012.195297 · 7.91 Impact Factor
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