Nano delivery of MiR-146a and its effect study on genes involved in apoptosis and autophagy pathways in lung cancer and tuberculosis.

Abstract

Background: Tuberculosis (TB) and lung cancer (LC) are among the leading causes of death worldwide and present serious challenges in diagnosis and treatment. Therefore, developing new strategies for their treatment is crucial. MicroRNAs (miRNAs) are biological molecules that play a critical role in regulating essential processes, such as apoptosis and autophagy, in TB and LC by targeting specific genes. Recently, carbon nanotubes functionalized with Polyethyleneimine (CNT-PEI) to deliver miRNAs to target cells have been investigated to enhance therapeutic effects.

Methods: In this study, miR-146a was transfected into LC (A549), macrophages infected with TB (THP1), and healthy lung cells (MRC5) using CNT-PEI. Then, the expression of miR-146a and its target gene, TNF receptor-associated factor-6 (TRAF6), and other genes involved in apoptosis and autophagy pathways including BCL-2, IL-6, tumor necrosis factor-alpha (TNFα), were measured using Real-Time PCR. Finally, the effect of overexpression of miR-146a on these genes was investigated in all three cell lines.

Result: The results showed successful transfection of miR-146a using the CNT-PEI nano delivery system in LC and TB cell models. Then, increased expression of miR-146 increased apoptosis and autophagy by targeting the TRAF6 gene and affecting other genes such as BCL-2, IL-6, and TNFα through the NF-kB signaling pathway.

Conclusion: The findings suggest an important role for miR-146a in TB and LC, which regulates inflammatory responses and treats these diseases. However, further studies are needed on using CNT-PEI in vivo, as well as the balance between local anti-inflammatory and non-inflammatory factors.