Sequential changes in expression of  long non-coding RNAs THRIL and MALAT1 after ischemic stroke

Mahnaz Bayat; Etrat Hooshmandi; Najmeh Karimi; Moosa Rahimi; Reza Tabrizi; Tahereh Asadabadi; Mohammad Saied Salehi; Seyedeh Shaghayegh Zafarmand; Maryam Owjfard; Carlos Garcia Esperon; Neil Spratt; Christopher Levi; Afshin Borhani-Haghighi

doi:10.18502/cjn.v23i1.16437

Mahnaz Bayat Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Etrat Hooshmandi Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Najmeh Karimi Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Moosa Rahimi Laboratory of Basic Sciences, Mohammad Rasul Allah Research Tower, Shiraz University of Medical Sciences, Shiraz, Iran
Reza Tabrizi Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
Tahereh Asadabadi Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Mohammad Saied Salehi Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Seyedeh Shaghayegh Zafarmand Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Maryam Owjfard Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Carlos Garcia Esperon Department of Neurology, John Hunter Hospital, Newcastle, Newcastle, Australia
Neil Spratt Department of Neurology, John Hunter Hospital, Newcastle, Newcastle, Australia
Christopher Levi Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia
Afshin Borhani-Haghighi Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, IranClinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

DOI: https://doi.org/10.18502/cjn.v23i1.16437

Keywords: Long Noncoding RNA; MALAT1 Long Noncoding RNA; THRIL Long Noncoding RNA; Ischemic Stroke

Abstract

Background: Inflammation is the major contributor to the pathophysiology of ischemic stroke (IS). Long
non-coding ribonucleic acids (lncRNAs) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and tumor necrosis factor and heterogeneous nuclear ribonucleoprotein L-related immunoregulatory (THRIL) have been demonstrated to be up-regulated in inflammation and atherosclerosis. Therefore, we aimed to study the expression profile of these lncRNAs after IS.

Methods: This observational case-control study was conducted in Namazi Hospital, Shiraz, Iran. The real-time polymerase chain reaction (RT-PCR) measured the sequential changes in circulating levels of MALAT1 and THRIL on days 1, 3, and 5 after IS. The receiver operating characteristic (ROC) curve analysis was used to estimate the diagnostic and prognostic potential of lncRNAs with the area under the curve (AUC).

Results: In patients with IS, the relative MALAT1 and THRIL expressions were significantly higher than the controls (P < 0.001 and P < 0.01, respectively), on days 1, 3, and 5 after stroke. We showed a significantly increase in lncRNAs expression on day five compared to days 1 and 3 after stroke. Moreover, a positive correlation was detected between MALAT1 expression and time within the first 24 hours after stroke (r = 0.27, P = 0.03). Logistic regression analysis showed a significant positive association between MALAT1 and THRIL and the risk of stroke evolution. We found a potential diagnostic marker for MALAT1 with an AUC of 0.78.

Conclusion: We demonstrated the significant sequential upregulation in MALAT1 and THRIL expression on days 1, 3, and 5 after IS with a significant positive association with the risk of stroke. MALAT1 also significantly correlated with time within the first 24 hours after stroke.