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Study and Characterization of Long Non-coding RUNX1-IT1 among Large Artery Atherosclerosis Stroke Patients Based on the ceRNA Hypothesis

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Abstract

Recent studies have shed light on the involvement of long non-coding RNAs (lncRNAs) in the initiation and development of stroke. However, the regulatory function of many lncRNAs in large artery atherosclerosis (LAA) has not been fully elucidated. Based on the competing endogenous RNA (ceRNA) hypothesis recently proposed by Pandolfi, the present study was conducted using experimental techniques and bioinformatics to investigate the expression and regulatory function of a lncRNA involved in the development of LAA. The lncRNAs differentially expressed in stroke were obtained using meta-analysis, and one lncRNA was selected for experimental studies on patients with LAA (n = 100) and healthy controls (n = 100) using quantitative real-time polymerase chain reaction (qRT-PCR). The patients were also evaluated through meta-analysis to identify the function of the selected lncRNA, miRNAs, and mRNAs with altered expression in stroke. Finally, the experimental results and meta-analysis findings were integrated, and different functional groups were assigned. The results indicated that the level of lncRNA-RUNX1-IT1 was significantly lower in the patients with LAA compared to the healthy control subjects (p > 0.05). Logistic regression analyses revealed that the expression of lncRNA-RUNX1-IT1 was inversely correlated with LAA (P = 009, OR = 0.871, 95% CI: 0.786–0.965). In addition, a network of differentially expressed genes (DE genes) was created for miRNAs and mRNAs based on their association with lncRNA-RUNX1-IT1. Functional analysis showed that the DE genes in the network are involved in the apoptosis and alternative splicing of RNAs. The findings of the present study suggest that the downregulation of lncRNA-RUNX1-IT1 is associated with LAA development by interrupting the regulatory network of cells. The results of network analysis demonstrated that the lncRNA-RUNX1-IT1 could influence the expression of mRNAs and miRNAs involved in the apoptosis and alternative splicing of RNAs.

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Funding

The present study was supported by Sabzevar University of Medical Sciences (grant number: 394212163).

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Author notes

  1. Ali Fasihi and Hafez Heydari-Zarnagh contributed equally to this work.

Authors and Affiliations

  1. Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Ali Fasihi

  2. Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Hafez Heydari-Zarnagh, Mehrnaz Kafashzadeh, Seyed Elyas Meshkani & Shahin Ramazi

  3. Bioinformatics and Computational Biology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohmmadsaeid Zahedi

  4. Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohmmadsaeid Zahedi

  5. Iranian Research Center on Healthy Aging, Sabzevar of Medical Sciences, Sabzevar, Iran

    Maryam Goudarzian

Authors
  1. Ali Fasihi
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  2. Hafez Heydari-Zarnagh
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  3. Mohmmadsaeid Zahedi
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  4. Maryam Goudarzian
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  6. Seyed Elyas Meshkani
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  7. Shahin Ramazi
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Contributions

Ali Fasihi and Hafez Heydari-Zarnagh designed the study and collaborated in analyzing the data and writing the manuscript; Shahin Ramazi collaborated in designing the project, analyzing the data, and performing experiments; Mohmmadsaeid Zahedi collaborated in analyzing the data, performing the experiments, and improving the language of the manuscript; Seyed Elyas Meshkani collaborated in writing the manuscript and improving the language of the manuscript. Maryam Gudarzian and Mehrnaz Kafashzadeh collaborated in collecting samples and patient information.

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Correspondence to Shahin Ramazi.

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The authors declare no conflicts of interest with any organization regarding the materials dealt with in this paper.

Ethical Approval

Investigations on human participants were approved by the Sabzevar University Health Research Ethics Committee. The authors of the present study did not perform any investigation on animals.

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Fasihi, A., Heydari-Zarnagh, H., Zahedi, M. et al. Study and Characterization of Long Non-coding RUNX1-IT1 among Large Artery Atherosclerosis Stroke Patients Based on the ceRNA Hypothesis. J Mol Neurosci 71, 455–465 (2021). https://doi.org/10.1007/s12031-020-01668-8

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  • DOI: https://doi.org/10.1007/s12031-020-01668-8

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