Histone Deacetylase 6 Inhibitor Suppresses The Inflammation Through MIR17HG In LPS-Induced Macrophages

Background: Long non-coding RNAs (lncRNAs) have been linked to a wide range of pathologic diseases despite having a limited capacity for protein coding. MIR17HG is the host gene for the miR17-92a-1 cluster, a group of six microRNAs involved in several cellular functions. Dysregulation of MIR17HG has been associated with multiple diseases such as Feingold Syndrome, osteoarthritis, Parkinson’s disease, and cancer. Treatment with histone deacetylase-6 inhibitor (Tubastatin A -TBA) reduces inflammatory response on macrophages after LPS challenge. Here, we analyze the role of MIR17HG as an epigenetic regulator of inflammation in LPS-induced THP1 cells. Hypothesis: We hypothesize that TBA suppresses the effect of MIR17HG and promotes protection in macrophages under LPS-induced inflammation. Methods and Results: To elucidate potential lncRNAs of interest during macrophage inflammatory response, we treated macrophages with LPS (1 μg/mL) and TBA (2.5 μM) for 1hr and performed RNA sequencing. We selected MIR17HG for further investigation based on the sequencing data (Fig. A) and bioinformatic analysis. The expression of MIR17HG in LPS and TBA treatment conditions was validated by qRT-PCR. MIR17HG expression was significantly higher in LPS and treatment with TBA suppressed the LPS-stimulated MIR17HG expression (Fig. B, C) . We also observed the IL1β behaved in a similar manner (Fig. D) . Further overexpression and knockdown experiments will be performed to identify the link between MIR17HG and ILβ. Conclusion: We report for the first time that MIR17HG is an important mediator of the pro-inflammatory response of macrophages.