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Abnormal expression of long non-coding RNAs RMRP, CTC-487M23.5, and DGCR5 in the peripheral blood of patients with Bipolar disorder

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Abstract

Long non-coding RNAs (lncRNAs) have been recently considered as one of the regulatory mechanisms of the nervous system. Hence, lncRNAs may be considered diagnostic biomarkers for bipolar disorder (BD). We aimed to investigate the expression of RMRP, CTC-487M23.5, and DGCR5 lncRNAs in bipolar patients. The levels of these three lncRNAs were measured in peripheral blood mononuclear cells (PBMCs) of 50 BD patients and 50 healthy subjects by real-time PCR. Moreover, we performed a ROC curve analysis between the gene expression and some clinical features of BD patients. Significant upregulation of RMRP and CTC-487M23.5 and no significant change in levels of DGCR5 was observed in BD individuals compared with controls. Also, we found upregulation of RMRP and downregulation of CTC-487M23.5 and DGCR5 in females with BD. The areas under the ROC curve (AUC) for RMRP and CTC-487M23.5 lncRNAs were 0.80 and 0.61, respectively. There was no significant correlation between the expression of these three lncRNAs and clinical features in PBMCs of BD patients. These results suggest a role for RMRP and CTC-487M23.5 in the pathogenesis of bipolar disorder. Moreover, the peripheral expression of these two lncRNAs might be beneficial as potential biomarkers for BD.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Akbari M, Eghtedarian R, Hussen BM, Eslami S, Taheri M, Neishabouri SM, Ghafouri-Fard S (2022) Assessment of expression of regulatory T cell differentiation genes in autism spectrum disorder. Front Mol Neurosci 15

  • Baruah C, Nath P, Barah P (2022a) LncRNAs in neuropsychiatric disorders and computational insights for their prediction. Mol Biol Rep 49:11515–11534

    Article  CAS  PubMed  Google Scholar 

  • Borzo G, Emanuel G, Buhe N, Alex M, Katherine M, Stephanie S, Rahuman SMS, Alessandro C, Joana C, Emma N, Holger K, Ian R, Petra H, Pedro B, Silvia DMS (2020) A FGF2-mediated incoherent feedforward loop induces Erk inhibition and promotes naïve pluripotency. bioRxiv 2020:2020.11.11.378869

  • Centofanti F, Santoro M, Marini M, Visconti VV, Rinaldi AM, Celi M, D’Arcangelo G, Novelli G, Orlandi A, Tancredi V, Tarantino U, Botta A (2020) Identification of Aberrantly-Expressed Long Non-Coding RNAs in Osteoblastic Cells from Osteoporotic Patients. Biomedicines 8:65

    Article  PubMed  PubMed Central  Google Scholar 

  • Dacquino C, de Rossi P, Spalletta G (2015) Schizophrenia and bipolar disorder: The road from similarities and clinical heterogeneity to neurobiological types. Clin Chim Acta 449:49–59

    Article  CAS  PubMed  Google Scholar 

  • Duan Y, Jia Y, Wang J, Liu T, Cheng Z, Sang M, Lv W, Qin J, Liu L (2021) Long noncoding RNA DGCR5 involves in tumorigenesis of esophageal squamous cell carcinoma via SRSF1-mediated alternative splicing of Mcl-1. Cell Death Dis 12:587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • García-Fonseca Á, Martin-Jimenez C, Barreto GE, Pachón AFA, González J (2021) The Emerging Role of Long Non-Coding RNAs and MicroRNAs in Neurodegenerative Diseases: A Perspective of Machine Learning. Biomolecules 11(8):1132

    Article  PubMed  PubMed Central  Google Scholar 

  • Ghafouri-Fard S, Badrlou E, Taheri M, Dürsteler KM, Beatrix Brühl A, Sadeghi-Bahmani D, Brand S (2021) A comprehensive review on the role of non-coding RNAs in the pathophysiology of bipolar disorder. Int J Mol Sci 22:5156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gharibi B, Gonçalves E, Nashun B, Montoya A, Mankalow K, Strohbuecker S, Sheriff RS, Cicarrelli A, Carvalho J, Nye E, Kramer H (2020) A FGF2-mediated incoherent feedforward loop induces Erk inhibition and promotes naïve pluripotency. BioRxiv, pp 2020–2011

  • Hao WZ, Chen Q, Wang L, Tao G, Gan H, Deng LJ, Huang JQ, Chen JX (2022) Emerging roles of long non-coding RNA in depression. Prog Neuropsychopharmacol Biol Psychiatry 115:110515

    Article  CAS  PubMed  Google Scholar 

  • Harrison PJ, Cipriani A, Harmer CJ, Nobre AC, Saunders K, Goodwin GM, Geddes JR (2016) Innovative approaches to bipolar disorder and its treatment. Ann N Y Acad Sci 1366:76–89

    Article  PubMed  PubMed Central  Google Scholar 

  • Hayes JF, Marston L, Walters K, King MB, Osborn DPJ (2017) Mortality gap for people with bipolar disorder and schizophrenia: UK-based cohort study 2000–2014. Br J Psychiatry 211:175–181

    Article  PubMed  PubMed Central  Google Scholar 

  • Hermanns P, Bertuch AA, Bertin TK, Dawson B, Schmitt ME, Shaw C, Zabel B, Lee B (2005) Consequences of mutations in the non-coding RMRP RNA in cartilage-hair hypoplasia. Hum Mol Genet 14:3723–3740

    Article  CAS  PubMed  Google Scholar 

  • Hong H, Xu G, Chen J, Zhang J, Chen C, Wu C, Jiang J, Cui Z (2022) LncRNA RMRP Contributes to the Development and Progression of Spinal Cord Injury by Regulating miR-766-5p/FAM83A Axis. Mol Neurobiol 59:6200–6210

    Article  CAS  PubMed  Google Scholar 

  • Hongfeng Z, Andong J, Liwen S, Mingping B, Xiaowei Y, Mingyong L, Aimin Y (2020) lncRNA RMRP knockdown suppress hepatocellular carcinoma biological activities via regulation miRNA-206/TACR1. J Cell Biochem 121:1690–1702

    Article  PubMed  Google Scholar 

  • Huang H, Yang X, Chen J, Fu J, Chen C, Wen J, Mo Q (2019) lncRNA DGCR5 inhibits the proliferation of colorectal cancer cells by downregulating miR-21. Oncol Lett 18:3331–3336

    CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson R (2012) Long non-coding RNAs in Huntington’s disease neurodegeneration. Neurobiol Dis 46:245–54

    Article  CAS  PubMed  Google Scholar 

  • Johnson R, Teh CH, Jia H, Vanisri RR, Pandey T, Lu ZH, Buckley NJ, Stanton LW, Lipovich L (2009) Regulation of neural macroRNAs by the transcriptional repressor REST. RNA 15:85–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jovčevska I, VidetičPaska A (2021) Neuroepigenetics of psychiatric disorders: Focus on lncRNA. Neurochem Int 149:105140

    Article  PubMed  Google Scholar 

  • Liu S, Chu B, Cai C, Wu X, Yao W, Wu Z, Yang Z, Li F, Liu Y, Dong P, Gong W (2020a) DGCR5 Promotes Gallbladder Cancer by Sponging MiR-3619-5p via MEK/ERK1/2 and JNK/p38 MAPK Pathways. J Cancer 11:5466–5477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu S, Lai W, Shi Y, Liu N, Ouyang L, Zhang Z, Chen L, Wang X, Qian B, Xiao D, Yan Q, Cao Y, Liu S, Tao Y (2020) Annotation and cluster analysis of long noncoding RNA linked to male sex and estrogen in cancers. NPJ Precis Oncol 4:5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  • Malcolm JR, Leese NK, Lamond-Warner PI, Brackenbury WJ, White RJ (2022) Widespread association of ERα with RMRP and tRNA genes in MCF-7 cells and breast cancers. Gene 821:146280

    Article  CAS  PubMed  Google Scholar 

  • Meinhard N, Kessing LV, Vinberg M (2014) The role of estrogen in bipolar disorder, a review. Nord J Psychiatry 68:81–87

    Article  PubMed  Google Scholar 

  • Meng Q, Wang K, Brunetti T, Xia Y, Jiao C, Dai R, Fitzgerald D, Thomas A, Jay L, Eckart H, Grennan K, Imamura-Kawasawa Y, Li M, Sestan N, White KP, Chen C, Liu C (2018) The DGCR5 long noncoding RNA may regulate expression of several schizophrenia-related genes. Sci Transl Med 10(472)

  • Pan J, Zhang D, Zhang J, Qin P, Wang J (2019) LncRNA RMRP silence curbs neonatal neuroblastoma progression by regulating microRNA-206/tachykinin-1 receptor axis via inactivating extracellular signal-regulated kinases. Cancer Biol Ther 20:653–665

    Article  CAS  PubMed  Google Scholar 

  • Pirbalouti RG, Mohseni MM, Taheri M, Neishabouri SM, Shirvani-Farsani Z (2023) Deregulation of NF-κB associated long non-coding RNAs in bipolar disorder. Metab Brain Dis 38(7):2223–2230

    Article  CAS  PubMed  Google Scholar 

  • Sayad A, Taheri M, Omrani MD, Fallah H, KholghiOskooei V, Ghafouri-Fard S (2019) Peripheral expression of long non-coding RNAs in bipolar patients. J Affect Disord 249:169–174

    Article  CAS  PubMed  Google Scholar 

  • Sher L (2023) Testosterone and Suicidal Behavior in Bipolar disorder. Int J Environ Res Public Health 20(3)

  • Song HK, Kim SY (2021) The Role of Sex-specific Long Non-coding RNAs in Cancer Prevention and Therapy. J Cancer Prev 26:98–109

    Article  PubMed  PubMed Central  Google Scholar 

  • Tang ZB, Chen HP, Zhong D, Song JH, Cao JW, Zhao MQ, Han BC, Duan Q, Sheng XM, Yao JL, Li GZ (2022) LncRNA RMRP accelerates autophagy-mediated neurons apoptosis through miR-3142/TRIB3 signaling axis in alzheimer’s disease. Brain Res 1785:147884

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Wang L, Ding Y, Lu X, Zhang G, Yang J, Zheng H, Wang H, Jiang Y, Xu L (2017) LncRNA structural characteristics in epigenetic regulation. Int J Mol Sci 18(12)

  • Wei L, Peng Y, Yang XJ, Zhou P (2021) Knockdown of long non-coding RNA RMRP protects cerebral ischemia-reperfusion injury via the microRNA-613/ATG3 axis and the JAK2/STAT3 pathway. Kaohsiung J Med Sci 37:468–478

    Article  CAS  PubMed  Google Scholar 

  • Wooderson SC, Gallagher P, Watson S, Young AH (2015) An exploration of testosterone levels in patients with bipolar disorder. Bjpsych Open 1:136–138

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu X, Hou P, Qiu Y, Wang Q, Lu X (2020) Large-Scale Analysis Reveals the Specific Clinical and Immune Features of DGCR5 in Glioma. Onco Targets Ther 13:7531–7543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshino Y, Dwivedi Y (2020) Non-Coding RNAs in Psychiatric Disorders and Suicidal Behavior. Front Psychiatry 11:543893

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang M, He P, Bian Z (2021) Long noncoding RNAs in neurodegenerative diseases: pathogenesis and potential implications as clinical biomarkers. Front Mol Neurosci 14

  • Zhou Y, Lutz P-E, Wang YC, Ragoussis J, Turecki G (2018) Global long non-coding RNA expression in the rostral anterior cingulate cortex of depressed suicides. Transl Psychiatry 8:224

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou N, He Z, Tang H, Jiang B, Cheng W (2019a) LncRNA RMRP/miR-613 axis is associated with poor prognosis and enhances the tumorigenesis of hepatocellular carcinoma by impacting oncogenic phenotypes. Am J Transl Res 11:2801–2815

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou L, Yu X, Guo Y, Liu X (2022) LncRNA RMRP knockdown promotes proliferation and migration of Schwann cells by mediating the miR-766-5p/CAND1 axis. Neurosci Lett 770:136440

    Article  CAS  PubMed  Google Scholar 

  • Zhou Z, Xu H, Liu B, Dun L, Lu C, Cai Y, Wang H (2019b) Suppression of lncRNA RMRP ameliorates oxygen-glucose deprivation/re-oxygenation-induced neural cells injury by inhibiting autophagy and PI3K/Akt/mTOR-mediated apoptosis. Biosci Rep 39(6)

  • Zhou Y (2017) The role of long non-coding RNAs in the depressed brain. McGill University

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Acknowledgements

The authors would like to thank the clinical Research Development Unit (CRDU) of Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran for their support, cooperation and assistance throughout the period of study.

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Authors

Contributions

MG and MM-M wrote the manuscript, collected the data, and revised it. ZS-F and MT designed the study, revised and supervised it. SMA collected the samples data and analysed them. All authors approved this manuscript.

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Correspondence to Mohammad Taheri, Seyedeh Morvarid Neishabouri or Zeinab Shirvani-Farsani.

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All procedures were in accordance with the ethical standards of national research committee and with the 1964 Helsinki declaration. Informed consent forms were obtained from all study participants. The study protocol was approved by the ethical committee of Shahid Beheshti University of Medical Sciences.

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Ghamari, M., Mehrab Mohseni, M., Taheri, M. et al. Abnormal expression of long non-coding RNAs RMRP, CTC-487M23.5, and DGCR5 in the peripheral blood of patients with Bipolar disorder. Metab Brain Dis 39, 313–320 (2024). https://doi.org/10.1007/s11011-023-01316-1

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