Serum miR-30c-5p is a potential biomarker for multiple system atrophy

Abstract

Multiple system atrophy (MSA) is a neurodegenerative disease that belongs to the α synucleinopathies. Clinically, there is an overlap between MSA and Parkinson’s disease (PD), especially at the early disease stage. However, these two pathologies differ in terms of disease progression. Currently, no biomarker exists to differentiate MSA from PD. MicroRNAs are non-coding RNAs implicated in gene expression regulation. MiRNAs modulate cellular activity and they control a range of physiological and pathological functions. miRNAs are found in biofluids, such as blood, serum, plasma, saliva, and cerebrospinal fluid. Many groups, including ours, found that circulating miRNAs are differently expressed in blood, plasma, serum and cerebrospinal fluid of PD and MSA patients. In the present study, our primary aim was to determine if serum mir-30-5p and mir-148b-5p can be used as biomarkers for early diagnosis of PD and/or MSA. Our secondary goal was to determine if serum levels of those miRNAs can be correlated with the patients’ clinical profile. Using quantitative PCR (qPCR), we evaluated expression levels of miR-30c-5p and miR148b-5p in serum samples from PD (n = 56), MSA (n = 49), and healthy control (n = 50) subjects. We have found that miR-30c-5p is significantly upregulated in MSA if compared with PD and healthy control subjects. Moreover, serum miR-30c-5p levels correlate with disease duration in both MSA and PD. No significant difference was found in miR-148b-5p among MSA, PD and healthy control subjects. Our results suggest a possible role of serum miR-30-5p as a biomarker for diagnosis and progression of MSA.

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References

  1. 1.

    Brai E et al (2016) Notch1 hallmarks fibrillary depositions in sporadic Alzheimer’s disease. Acta Neuropathol Commun 4(1):64

    Article  Google Scholar 

  2. 2.

    Cardo LF et al (2013) Profile of microRNAs in the plasma of Parkinson’s disease patients and healthy controls. J Neurol 260(5):1420–1422

    Article  Google Scholar 

  3. 3.

    Choubey V et al (2014) BECN1 is involved in the initiation of mitophagy: it facilitates PARK2 translocation to mitochondria. Autophagy 10(6):1105–1119

    CAS  Article  Google Scholar 

  4. 4.

    De Smaele E, Ferretti E, Gulino A (2010) MicroRNAs as biomarkers for CNS cancer and other disorders. Brain Res 1338:100–111

    Article  Google Scholar 

  5. 5.

    Desplats P et al (2011) α-Synuclein sequesters Dnmt1 from the nucleus: a novel mechanism for epigenetic alterations in Lewy body diseases. J Biol Chem 286(11):9031–9037

    CAS  Article  Google Scholar 

  6. 6.

    Galvin JE, Lee VM, Trojanowski JQ (2001) Synucleinopathies: clinical and pathological implications. Arch Neurol 58:186–190

    CAS  Article  Google Scholar 

  7. 7.

    Grasso M, Piscopo P, Confaloni A, Denti MA (2014) Circulating miRNAs as biomarkers for neurodegenerative disorders. Molecules 19(5):6891–6910

    Article  Google Scholar 

  8. 8.

    Hossein-nezhad A et al (2016) Transcriptomic profiling of extracellular RNAs present in cerebrospinal fluid identifies differentially expressed transcripts in Parkinson’s disease. J Parkinson’s Dis 6(1):109–117

    CAS  Article  Google Scholar 

  9. 9.

    Jankovic J, Tolosa E (eds) (1998) Parkinson’s disease movement disorders, vol 8, pp 159–171

  10. 10.

    Khoo SK et al (2012) Plasma-based circulating microRNA biomarkers for Parkinson’s disease. J Parkinson’s Dis 2(4):321–331. 12

    CAS  Google Scholar 

  11. 11.

    Kume K et al (2018) Serum microRNA expression profiling in patients with multiple system atrophy. Mol Med Rep 17(1):852–860

    CAS  PubMed  Google Scholar 

  12. 12.

    Laurens B et al (2015) Fluid biomarkers in multiple system atrophy: a review of the MSA biomarker initiative. Neurobiol Dis 80:29–41

    Article  Google Scholar 

  13. 13.

    Marques TM et al (2017) MicroRNAs in cerebrospinal fluid as potential biomarkers for Parkinson’s disease and multiple system atrophy. Mol Neurobiol 54(10):7736–7745

    CAS  Article  Google Scholar 

  14. 14.

    Merwe et al (2015) Evidence for a common biological pathway linking three Parkinson’s disease causing genes: parkin, PINK1 and DJ1. Eur J Neurosci 41(9):1113–1125

    Article  Google Scholar 

  15. 15.

    Michiorri S et al (2010) The Parkinson-associated protein PINK1 interacts with Beclin1 and promotes autophagy. Cell Death Differ 17(6):962–974

    CAS  Article  Google Scholar 

  16. 16.

    Nadim WD et al (2017) MicroRNAs in neurocognitive dysfunctions: new molecular targets for pharmacological treatments? Curr Neuropharmacol 15(2):260–275

    CAS  Article  Google Scholar 

  17. 17.

    Pickford F et al (2008) The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice. J Clin Invest 118(6):2190

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Quévillon Huberdeau M, Simard MJ (2018) A guide to microRNA-mediated gene silencing. FEBS J. https://doi.org/10.1111/febs.14666

  19. 19.

    Serpente M et al (2015) Profiling of ubiquitination pathway genes in peripheral cells from patients with frontotemporal dementia due to C9ORF72 and GRN mutations. Int J Mol Sci 16(1):1385–1394

    CAS  Article  Google Scholar 

  20. 20.

    Son JH et al (2012) Neuronal autophagy and neurodegenerative diseases. Exp Mol Med 44(2):89–98

    CAS  Article  Google Scholar 

  21. 21.

    Song C et al (2011) Paraquat induces epigenetic changes by promoting histone acetylation in cell culture models of dopaminergic degeneration. Neurotoxicology 32(5):586–595

    CAS  Article  Google Scholar 

  22. 22.

    Vallelunga A et al (2014) Identification of circulating microRNAs for the differential diagnosis of Parkinson’s disease and multiple system atrophy. Front Cell Neurosci 8:156

    Article  Google Scholar 

  23. 23.

    Wang JD et al (2015) A pivotal role of FOS-mediated BECN1/Beclin 1 upregulation in dopamine D2 and D3 receptor agonistinduced autophagy activation. Autophagy 11(11):2057–2073

    CAS  Article  Google Scholar 

  24. 24.

    Wenning GK et al (1994) Clinical features and natural history of multiple system atrophy: an analysis of 100 cases. Brain 117:835–845

    Article  Google Scholar 

  25. 25.

    Wu Q et al (2017) Nuclear accumulation of histone deacetylase 4 (HDAC4) exerts neurotoxicity in models of Parkinson’s disease. Mol Neurobiol 54(9):6970–6983

    CAS  Article  Google Scholar 

  26. 26.

    Yoon JH et al (2017) Parkin mediates neuroprotection through activation of Notch1 signaling. Neuroreport 28(4):181–186

    CAS  Google Scholar 

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Correspondence to Annamaria Vallelunga.

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Vallelunga, A., Iannitti, T., Dati, G. et al. Serum miR-30c-5p is a potential biomarker for multiple system atrophy. Mol Biol Rep 46, 1661–1666 (2019). https://doi.org/10.1007/s11033-019-04614-z

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Keywords

  • Parkinson’s disease
  • MiRNAs
  • Multiple system atrophy
  • MiR-30c-5p
  • Biomarker
  • Synucleinopathies