The Possible Regulatory Mechanism of SLCO۱B۱ Expression

Background and Aim: ۲۵% of all deaths in industrialized countries result from arterial blockage caused by atherosclerotic plaques which are related to high cholesterol-carrying low-density lipoprotein, LDL-C. To overcome cardiovascular morbidity which is one of the most prominent causes of all deaths around the world it is trustworthy to manage lipid profiles. Statins are lipid-lowering drugs that inhibit HMGCR, the rate-limiting enzyme in the cholesterol biosynthetic pathway. SLCO۱B۱ is a liver-specific member of the organic anion transporter family which is involved in the removal of drug compounds such as statins from the blood into the hepatocytes where statins elicit desired effects. It is advantageous to study the regulatory mechanism of SLCO۱B۱ expression. A new era in molecular biology revealed non-coding RNAs as post-ranscriptional regulators. miRNAs fall into the same category and control gene expression by binding to the ۳’UTR of mRNA transcripts.Methods: By literature review, we have found some miRNAs (hsa-miR-۱۹۲, hsa-miR-۳۳a, hsa-miR-۲۲۱, hsa-miR-۱۴۸a, hsa-miR-۱۴۸a) that their expressions are influenced by statins treatment in the liver thus it is interesting to find out whether these miRNAs are involved in the regulatory mechanism of SLCO۱B۱ expression or not. In this study, we have assayed the miRNAs-mRNAs interaction by Rnahybrid which is a bioinformatics tool for finding the minimum free energy hybridization of a long and short RNA http://bibiserv.cebitec.uni-bielefeld.de/rnahybrid. Results: By Rnahybrid it is determined that the maximum free energy (MEF) for each interaction between SLCO۱B۱ transcript (NM_۰۰۶۴۴۶.۵) and miRNAs (hsa-miR-۱۹۲-۵p, hsa-miR-۳۳a-۵p, hsa-miR-۳۳a-۳p,hsa-miR-۲۲۱-۵p, hsa-miR-۱۴۸a-۳p, hsa-miR-۱۵a-۳p) are -۱۷, -۱۹.۸, -۲۲.۷, -۱۸.۴, -۱۹, - ۲۰.۸ respectively.Conclusion: The analysis shows that these miRNAs may regulate SLCO۱B۱ expression. At the end it is recommended to validate this analysis by more experiments.

کلیدواژه ها:

Statins ، Cardiovascular diseases ، SLCO۱B۱ ، miRNAs