RESUMO
Circulating cell-free miRNAs (ccf-miRs) have gained significant interest as biomarkers for lung cancer (LC) diagnosis. However, the clinical application of ccf-miRs is mainly limited by time, cost, and expertise-related problems of existing detection strategies. Recently, the development of different point-of-care (POC) approaches offers useful on-site platforms, because these technologies have important features such as portability, rapid turnaround time, minimal sample requirement, and cost-effectiveness. In this review, we discuss different POC approaches for detecting ccf-miRs and highlight the utility of incorporating nanomaterials for enhanced biorecognition and signal transduction, further improving their diagnostic applicability in LC settings.
Assuntos
MicroRNA Circulante/genética , Neoplasias Pulmonares/diagnóstico , Testes Imediatos , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , Humanos , Neoplasias Pulmonares/genética , NanoestruturasRESUMO
Polycyclic aromatic hydrocarbons (PAHs) refer to a ubiquitous group of anthropogenic air pollutants that are generated through incomplete carbon combustion. Although the immunotoxic nature of PAHs has been previously reported, the underlying molecular mechanisms of this effect are not fully understood. In the present study, we investigated the mitochondrial-mediated epigenetic regulation of 2 PAHs, carcinogenic (benzo[a]pyrene; BaP) and noncarcinogenic (anthracene [ANT]), in peripheral lymphocytes. While ANT exposure triggered mitochondrial oxidative damage, no appreciable epigenetic modifications were observed. On the other hand, exposure to BaP perturbed the mitochondrial redox machinery and initiated cascade of epigenetic modifications. Cells exposed to BaP showed prominent changes in the expression of mitochondrial microRNAs (miR-24, miR-34a, miR-150, and miR-155) and their respective gene targets (NF-κß, MYC, and p53). The exposure of BaP also caused significant alterations in the expression of epigenetic modifiers (DNMT1, HDAC1, HDAC7, KDM3a, EZH2, and P300) and hypomethylation within nuclear and mitochondrial DNA. This further induced methylation of histone tails, which play a crucial role in the regulation of chromatin structure. Overall, our study provides novel mechanistic insights into the mitochondrial regulation of epigenetic modifications in association with PAH-induced immunotoxicity.
