MicroRNA-34a Encapsulated in Hyaluronic Acid Nanoparticles Induces Epigenetic Changes with Altered Mitochondrial Bioenergetics and Apoptosis in Non-Small-Cell Lung Cancer Cells.

摘要: Therapies targeting epigenetic changes for cancer treatment are in Phase I/II trials; however, all of these target only nuclear DNA. Emerging evidence suggests presence methylation marks on mitochondrial DNA (mtDNA); but their contribution is unidentified. Expression genes encoded mtDNA altered cells, along with increased glycolytic flux. Such flux and elevated reactive oxygen species supported by antioxidant; glutathione. MicroRNA-34a can translocate to mitochondria, mediate downstream apoptotic effects tumor suppressor P53, inhibit the antioxidant response element Nrf-2, resulting depleted glutathione levels. Based such strong rationale, we encapsulated microRNA-34a our well-established Hyaluronic-Acid nanoparticles delivered cisplatin-sensitive cisplatin-resistant A549-lung adenocarcinoma cells. Successful delivery uptake cells resulted ATP levels, decreased flux, Nrf-2 ultimately caspase-3 activation apoptosis. Most important were concurrent underlying molecular status D-loop transcription mtDNA-encoded genes. Although preliminary, provide a novel therapeutic approach form bioenergetics redox that subsequently results induction cell