Sheikhpour Mojgan, Maleki Mobina, Sakhi Hanie, Movafagh Abolfazl, Nojoumi Seyed Ali, Ghazizadeh Leila
Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran (IPI), No. 69, Pasteur Ave, Tehran, 1316943551, Iran.
Departments of Biosciences, University of Milano, Via Celoria 26, Milan, I-30133, Italy.
BMC Biotechnol. 2025 Aug 11;25(1):81. doi: 10.1186/s12896-025-01019-8.
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.
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.
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.
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.
结核病（TB）和肺癌（LC）是全球主要死因，在诊断和治疗方面面临严峻挑战。因此，开发新的治疗策略至关重要。微小RNA（miRNA）是一类生物分子，通过靶向特定基因在结核病和肺癌中调节细胞凋亡和自噬等重要过程中发挥关键作用。最近，已对用聚乙烯亚胺功能化的碳纳米管（CNT-PEI）将miRNA递送至靶细胞以增强治疗效果进行了研究。
在本研究中，使用CNT-PEI将miR-146a转染至肺癌细胞（A549）、感染结核的巨噬细胞（THP1）和健康肺细胞（MRC5）。然后，使用实时定量PCR测量miR-146a及其靶基因肿瘤坏死因子受体相关因子6（TRAF6）以及其他参与细胞凋亡和自噬途径的基因（包括BCL-2、白细胞介素6、肿瘤坏死因子-α（TNFα））的表达。最后，在所有三种细胞系中研究miR-146a过表达对这些基因的影响。
结果表明，在肺癌和结核细胞模型中，使用CNT-PEI纳米递送系统成功转染了miR-146a。然后，miR-146表达增加通过靶向TRAF6基因并通过NF-κB信号通路影响BCL-2、IL-6和TNFα等其他基因，从而增加细胞凋亡和自噬。
研究结果表明miR-146a在结核病和肺癌中发挥重要作用，其可调节炎症反应并治疗这些疾病。然而，需要进一步研究CNT-PEI在体内的应用以及局部抗炎和非炎症因子之间的平衡。
