LncRNA HOTAIR regulates the HMGCR Gene function in Atorvastatin HepG2 treated cells

Document Type : Original Research

Authors
S. Javanzad 1
S. Z. Azarshin 2
M. A. Boroumand 2
S. Sadeghian 2
M. Behmanesh 1
1 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
2 Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Introduction: Statins are one of the approved drugs used in the clinic, which are prescribed to reduce the amount of cholesterol in the blood of patients. However, the effects of the drug in reducing the amount of fat and the occurrence of side effects are not the same in the patients. Considering the role of LncRNAs in regulating gene expression, the possible role of HOTAIR LncRNA and atorvastatin treatment in regulating HMGCR gene expression as the main regulating gene in cholesterol synthesis has been investigated.

Methods: Bioinformatics analyses were used to find common regulatory factors between the HMGCR gene and candidate LncRNAs. MTT assay was used to determine the optimal dose of atorvastatin treatment on the HepG2 cell line. RNA extraction, cDNA synthesis, and quantitative analysis of gene expression were performed by qPCR. Finally, HMGCR protein expression was evaluated via the Western blot technique.

Results: Bioinformatic analyses showed that there is a relationship between HMGCR expression and some LncRNAs (HOTAIR, TUG1, MALAT1, GAS5, JPX, DLX6AS). In the cell culture, atorvastatin treatment increased the expression of HMGCR at mRNA and protein levels in the HepG2 cell line. Among the candidate lncRNAs, HOTAIR LncRNA expression decreased by 80% under atorvastatin treatment. Downregulating of the HOTAIR gene led to increased HMGCR gene expression at the RNA and protein levels.

Conclusion: The results of this study indicated that, aside from blocking the HMGCR enzyme binding site, atorvastatin can regulate the expression of HMGCR mRNA and protein by changing the HOTAIR expression.

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Subjects

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Pathobiology Reserach
Volume 26, Issue 1
November 2023
Pages 43-52