SpringerLink
Log in

Expression assay of calcium signaling related lncRNAs in autism

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Calcium signaling has essential roles in the neurodevelopmental processes and pathophysiology of related disorders for instance autism spectrum disorder (ASD).

Methods and results

We compared expression of SLC1A1, SLC25A12, RYR2 and ATP2B2, as well as related long non-coding RNAs, namely LINC01231, lnc-SLC25A12, lnc-MTR-1 and LINC00606 in the peripheral blood of patients with ASD with healthy children. Expression of SLC1A1 was lower in ASD samples compared with control samples (Expression ratio (95% CI) 0.24 (0.08–0.77), adjusted P value = 0.01). Contrary, expression of LINC01231 was higher in cases compared with control samples (Expression ratio (95% CI) 25.52 (4.19–154), adjusted P value = 0.0006) and in male cases compared with healthy males (Expression ratio (95% CI) 28.24 (1.91–418), adjusted P value = 0.0009). RYR2 was significantly over-expressed in ASD children compared with control samples (Expression ratio (95% CI) 4.5 (1.16–17.4), adjusted P value = 0.029). Then, we depicted ROC curves for SLC1A1, LINC01231, RYR2 and lnc-SLC25A12 transcripts showing diagnostic power of 0.68, 0.75, 0.67 and 0.59, respectively.

Conclusion

To sum up, the current study displays possible role of calcium related genes and lncRNAs in the development of ASD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

All data generated or analysed during this study are included in this published article [and its supplementary information files].

References

  1. Guerra DJ (2011) The molecular genetics of autism spectrum disorders: genomic mechanisms, neuroimmunopathology, and clinical implications. Autism Res Treat 2011:398636

    PubMed  PubMed Central  Google Scholar 

  2. Pourtavakoli A, Ghafouri-Fard S (2022) Calcium signaling in neurodevelopment and pathophysiology of autism spectrum disorders. Mol Biol Rep 49(11):10811–10823

    Article  CAS  PubMed  Google Scholar 

  3. Wei C-W, Luo T, Zou S-S, Wu A-S (2018) The role of long noncoding RNAs in central nervous system and neurodegenerative diseases. Front Behav Neurosci 12:175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Amadori E, Pellino G, Bansal L, Mazzone S, Møller RS, Rubboli G et al (2022) Genetic paroxysmal neurological disorders featuring episodic ataxia and epilepsy. Eur J Med Genet 65(4):104450

    Article  CAS  PubMed  Google Scholar 

  5. Mauri A, Duse A, Palm G, Previtali R, Bova SM, Olivotto S et al (2022) Molecular genetics of GLUT1DS Italian pediatric cohort: 10 novel disease-related variants and structural analysis. Int J Mol Sci 23(21):13560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Riza AL, Streață I, Roza E, Budișteanu M, Iliescu C, Burloiu C et al (2022) Phenotypic and genotypic spectrum of early-onset developmental and epileptic encephalopathies-data from a romanian cohort. Genes 13(7):1253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nesterova AP, Klimov EA, Zharkova M, Sozin S, Sobolev V, Ivanikova NV et al (2020) Chapter 5— diseases of the nervous system. In: Nesterova AP, Klimov EA, Zharkova M, Sozin S, Sobolev V, Ivanikova NV et al (eds) Disease pathways. Elsevier, Amsterdam, pp 219–258

    Chapter  Google Scholar 

  8. Wang X, Chen Z, Xu J, Tang S, An N, Jiang L et al (2022) SLC1A1-mediated cellular and mitochondrial influx of R-2-hydroxyglutarate in vascular endothelial cells promotes tumor angiogenesis in IDH1-mutant solid tumors. Cell Res 32(7):638–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu J, Yang A, Zhang Q, Yang G, Yang W, Lei H et al (2015) Association between genetic variants in SLC25A12 and risk of autism spectrum disorders: an integrated meta-analysis. Am J Med Genet Part B Neuropsychiatr Genet: Off Publ Int Soc Psychiatr Genet 168B(4):236–246

    Article  Google Scholar 

  10. Sakurai T, Ramoz N, Barreto M, Gazdoiu M, Takahashi N, Gertner M et al (2010) Slc25a12 disruption alters myelination and neurofilaments: a model for a hypomyelination syndrome and childhood neurodevelopmental disorders. Biol Psychiatry 67(9):887–894

    Article  CAS  PubMed  Google Scholar 

  11. Hopton C, Tijsen AJ, Maizels L, Arbel G, Gepstein A, Bates N et al (2022) Characterization of the mechanism by which a nonsense variant in RYR2 leads to disordered calcium handling. Physiol Rep 10(8):e15265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ficarella R, Di Leva F, Bortolozzi M, Ortolano S, Donaudy F, Petrillo M et al (2007) A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness. Proc Natl Acad Sci USA 104(5):1516–1521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Xu Z, Peng B, Liang Q, Chen X, Cai Y, Zeng S et al (2021) Construction of a ferroptosis-related Nine-lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma. Front Immunol 12:719175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ma J, Cui Z, Li B, Shi Y, Xu H, Chen J, Tang S (2018) Aberrant expression of long intergenic non-coding RNAs in the whole blood of patients with proliferative diabetic retinopathy. Investig Ophthalmol Vis Sci 59(9):1436

    Google Scholar 

  15. American psychiatric association Washington (2013) Diagnostic and statistical manual of mental disorders: DSM-5. American Psychiatric Association, Washington, DC

    Book  Google Scholar 

  16. Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC et al (2000) The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord 30(3):205–223

    Article  CAS  PubMed  Google Scholar 

  17. Nguyen RL, Medvedeva YV, Ayyagari TE, Schmunk G, Gargus JJ (2018) Intracellular calcium dysregulation in autism spectrum disorder: an analysis of converging organelle signaling pathways. Biochim Biophys Acta Mol Cell Res 1865(11 Pt B):1718–1732

    Article  CAS  PubMed  Google Scholar 

  18. Wilkinson B, Campbell DB (2013) Contribution of long noncoding RNAs to autism spectrum disorder risk. Int Rev Neurobiol 113:35–59

    Article  CAS  PubMed  Google Scholar 

  19. Taheri M, Pourtavakoli A, Eslami S, Ghafouri-Fard S, Sayad A (2023) Assessment of expression of calcium signaling related lncRNAs in epilepsy. Sci Rep 13(1):17993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Smits JJ, Oostrik J, Beynon AJ, Kant SG, de Koning Gans PA, Rotteveel LJ et al (2019) De novo and inherited loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment. Hum Genet 138:61–72

    Article  CAS  PubMed  Google Scholar 

  21. Scimemi A, Tian H, Diamond JS (2009) Neuronal transporters regulate glutamate clearance, NMDA receptor activation, and synaptic plasticity in the hippocampus. J Neurosci 29(46):14581–14595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Soueid J, Kourtian S, Makhoul NJ, Makoukji J, Haddad S, Ghanem SS et al (2016) RYR2, PTDSS1 and AREG genes are implicated in a Lebanese population-based study of copy number variation in autism. Sci Rep 6(1):1–11

    Article  Google Scholar 

  23. Liu X, Betzenhauser MJ, Reiken S, Meli AC, **e W, Chen B-X et al (2012) Role of leaky neuronal ryanodine receptors in stress-induced cognitive dysfunction. Cell 150(5):1055–1067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Smedler E, Kleppe J, Neufeld J, Lundin K, Bölte S, Landén M (2021) Cerebrospinal fluid and serum protein markers in autism: a co-twin study. J Neurochem 158(3):798–806

    Article  CAS  PubMed  Google Scholar 

  25. Oh DH, Kim IB, Kim SH, Ahn DH (2017) Predicting autism spectrum disorder using blood-based gene expression signatures and machine learning. Clin Psychopharmacol Neurosci 15(1):47–52

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was financially supported by Shahid Beheshti University of Medical Sciences.

Funding

The authors have not disclosed any funding.

Author information

Authors and Affiliations

  1. Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ashkan Pourtavakoli

  2. Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Soudeh Ghafouri-Fard

  3. Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

    Solat Eslami

  4. Center for Affective, Stress and Sleep Disorders, Psychiatric Clinics, University of Basel, Basel, Switzerland

    Serge Brand

  5. Institute of Human Genetics, Jena University Hospital, Jena, Germany

    Mohammad Taheri

  6. Urology and Nephrology Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Taheri

Authors
  1. Ashkan Pourtavakoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soudeh Ghafouri-Fard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Solat Eslami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Serge Brand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Taheri
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AP performed the experiment. SE analyzed the data. SGF wrote the draft and revised it. MT and SB designed and supervised the study. All the authors contribute equally and read the submission.

Corresponding authors

Correspondence to Soudeh Ghafouri-Fard or Mohammad Taheri.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethical approval

All procedures performed were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments.

Consent to participate

Informed consent forms were obtained from parents of all study participants. The study protocol was approved by the ethical committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.MSP.REC.1401.199).

Consent for publication

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pourtavakoli, A., Ghafouri-Fard, S., Eslami, S. et al. Expression assay of calcium signaling related lncRNAs in autism. Mol Biol Rep 51, 185 (2024). https://doi.org/10.1007/s11033-023-09182-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11033-023-09182-x

Keywords

Search

Navigation