Evidence Details for MIR339
PMID Title Journal Year Abstract
25695055 Acupuncture may exert its therapeutic effect through microRNA-339/Sirt2/NFkappaB/FOXO1 axis. Biomed Res Int. 2015;2015:249013. doi: 10.1155/2015/249013. Epub 2015 Jan 28. 2015 Recently, we have found that a number of microRNAs (miRNAs) and proteins are involved in the response to acupuncture therapy in hypertensive rats. Our bioinformatics study suggests an association between these miRNAs and proteins, which include miR-339 and sirtuin 2 (Sirt2). In this paper, we aimed to investigate whether Sirt2 was a direct target of miR-339 in neurons. In human SH-SY5Y cells, the luciferase assay implied that Sirt2 was likely a target of miRNA-339. Overexpression of miR-339 downregulated Sirt2 expression, while knockdown of miR-339 upregulated Sirt2 expression in human SH-SY5Y cells and rat PC12 cells. In addition, overexpression of miR-399 increased the acetylation of nuclear factor-kappaB (NF-kappaB) and forkhead box protein O1 (FOXO1) in SH-SY5Y cells, which are known targets of Sirt2. Our findings demonstrate that miR-339 regulates Sirt2 in human and rat neurons. Since Sirt2 plays a critical role in multiple important cellular functions, our data imply that acupuncture may act through epigenetic changes and subsequent action on their targets, such as miRNA-339/Sirt2/NF-kappaB/FOXO1 axis. Some physiological level changes of neurons after altering the miR-339 levels are needed to validate the suggested therapeutic role of miR-339/Sirt2/NF-kappaB/FOXO1 axis in response to acupuncture therapy in the future work."

Evidence Sentence: Acupuncture May Exert Its Therapeutic Effect through MicroRNA-339/Sirt2/NFkappaB/FOXO1 Axis
Evidence Sentence: Our bioinformatics study suggests an association between these miRNAs and proteins, which include miR-339 and sirtuin 2 (Sirt2).
Evidence Sentence: In this paper, we aimed to investigate whether Sirt2 was a direct target of miR-339 in neurons.
Evidence Sentence: Overexpression of miR-339 downregulated Sirt2 expression, while knockdown of miR-339 upregulated Sirt2 expression in human SH-SY5Y cells and rat PC12 cells.
Evidence Sentence: Our findings demonstrate that miR-339 regulates Sirt2 in human and rat neurons.
Evidence Sentence: Some physiological level changes of neurons after altering the miR-339 levels are needed to validate the suggested therapeutic role of miR-339/Sirt2/NF-kappaB/FOXO1 axis in response to acupuncture therapy in the future work.
Evidence Sentence: To validate whether Sirt2 is a likely target of miR-339, we performed computational miRNA target analysis, which showed that miRNA-339 was able to bind to the Sirt2 mRNA 3'-UTR, suggesting this gene might be a potential target for miRNA-339 (Figure 1(a)).
Evidence Sentence: Moreover, to examine whether miR-339 could repress Sirt2 expression through direct 3'-UTR interaction, we cloned Sirt2 3'-UTR luciferase reporter plasmid and performed reporter analysis in SH-SY5Y cells.
Evidence Sentence: Our present data demonstrated that cotransfection of miR-339 mimic with Sirt2 3'-UTR reporter resulted in dose-dependent inhibition of luciferase activity in SH-SY5Y cells (Figure 1(b), P < 0.05 versus control).
Evidence Sentence: However, miR-339 failed to repress the activity of Sirt2-3'-UTR reporter with a mutated miR-339 seed sequence (Figure 1(b)).
Evidence Sentence: These data indicated that Sirt2 was likely a direct target of miR-339.
Evidence Sentence: Our results showed that Sirt2 is the direct target of miR-339, indicating that miR-339 can contribute to an upregulation of the acetylated status of Sirt2 target, including NF-kappaB and FOXO1.
Evidence Sentence: In addition, overexpression of miR-399 increased the acetylation of nuclear factor-kappaB (NF-kappaB) and forkhead box protein O1 (FOXO1) in SH-SY5Y cells, which are known targets of Sirt2.