Abstract 19446: Role of miR-181 Family in the Heart: A Tale of Two Intracellular Compartments

• DOI: 10.1161/circ.132.suppl_3.19446
• Publication Date: 2021-07-03T04:10:04Z
• Authors: Samarjit Das; Mark J Kohr; Brittany Dunkerly; Djahida Bedja; Oliver A Kent; Anthony K Leung; Jorge Henao-Mejia; Richard A Flavell; Charles Steenbergen
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Recent reports suggest that mi(cro)RNAs, non-coding RNAs, can regulate numerous human genes. miRNAs play an important role in physiologic and pathologic processes of cardiovascular health. We identified a nuclear encoded miRNA (miR-181c) translocates into mitochondria to mitochondrial gene, ultimately affects function. To investigate how miR-181c leads cardiac injury, we designed miR-181-sponges, RNA molecules with ten repeated complimentary miR-181 “seed” sequences, generated set stable-H9c2 cells by transfecting either scrambled- or the miR-181-sponge-sequences. Sponge-H9c2 showed significant decrease ROS production reduced basal respiration, protection against Doxorubicin-induced oxidative stress. However, chronic down-regulation entire family also stimulates PTEN expression, thus sponge decreased PI3K signaling. Thus, Doxorubicin is enhanced when treated sponge-H9c2 siRNA PTEN. hypothesize miR-181a/b targets cytosol mt-COX1 mitochondria. extend this finding, miR-181a/b-/- miR-181c/d-/- mice were used. shows function at baseline compared both WT groups. Basal was significantly compare miR-181a/b-/-. Using Electron Microscopy light-scattering 540 nm isolated heart mitochondria, found are smaller , genomic DNA-qPCR number markedly higher 181a/b-/- decrease, while increase infarct size WT, hearts challenged ischemia-reperfusion injury. Taken together, regulates signaling pathways stress, notably detrimental results targeting (miR-181c), (miR-181a/b).