Post-transcriptional Regulation of PCSK9 by miR-191, miR-222, and miR-224

Abstract

Since proprotein convertase subtilisin kexin 9 (PCSK9) discovery, a gene involved in LDL metabolism regulation and cardiovascular diseases (CVD), many therapeutic strategies have been introduced for direct targeting of PCSK9. The main goal of these strategies has been to reduce PCSK9 protein level either by application of antibodies or inhibition of its production. In this study, we have tried to discover microRNAs (miRNAs) which can target, and hence regulate, PCSK9 expression. Using bioinformatics tools, we selected three microRNAs with binding sites on 3′-UTR of PCSK9. The expression level of these miRNAs was examined in three different cell lines using real-time RT-PCR. We observed a reciprocal expression pattern between expression level of miR-191, miR-222, and miR-224 with that of PCSK9. Accordingly, the expression levels were highest in Huh7 cells which expressed the lowest level of PCSK9, compared to HepG2 and A549 cell lines. PCSK9 mRNA level also showed a significant decline in HepG2 cells transfected with the vectors overexpressing the aforementioned miRNAs. Furthermore, the miRNAs target sites were cloned in psiCHECK-2 vector, and a direct interaction of the miRNAs and the PCSK9 3′-UTR putative target sites was investigated by means of luciferase assay. Our findings revealed that miR-191, miR-222, and miR-224 can directly interact with PCSK9 3′-UTR and regulate its expression. In conclusion, our data introduces a role for miRNAs to regulate PCSK9 expression.

RETRACTED: Downregulation of MicroRNA-222 Reduces Insulin Resistance in Rats with PCOS by Inhibiting Activation of the MAPK/ERK Pathway via Pten

“…Based on previous studies, there are miR-222-binding sites in PCSK9 , 15 MIA3 , 16 ABCG2 , 17 PUMA , 18 DKK2 , 19 and Pten . 20 To further evaluate it in the present study, miR-222 mimic or negative control (NC) mimic was transfected into 293A cells.…”

Genome‑wide integrated analysis demonstrates widespread functions of lncRNAs in mammary gland development and lactation in dairy goats

“…Fortunately, many studies have been performed to find their associated up/downstream mRNAs and antisense mRNAs related to lncRNAs. Functional annotation and enrichment are considered an effective way to reveal the biological significance and biological processes or functions of most enriched genes [28][29][30]. In this study, based on these basic principles, 2046 genes were scanned as apcGenes and antisense mRNAs for 883 lncRNAs, combined with the differentially expressed lncRNA, mRNAs and predicted pre-miRNA, as well as their interaction, and 1478 genes were detected and further served for GO enrichment and KEGG pathway analyses.…”

Nasal Microbiota Modifies the Effects of Particulate Air Pollution on Plasma Extracellular Vesicles

“…In particular, CD105+ EVs could probably promote vascular regeneration, either through a specific interaction or through miRNA delivering into recipient cells. Indeed, it has been found that CD105+ EVs-carried miRNA-222 may contribute to weaken inflammatory effects modulating the endothelial expression of ICAM-1 [47], as well as for the PCSK9 protein, which has been related as a biomarker for different cardiovascular negative conditions [48].…”