Background Lung cancer continues to be among the most fatal malignancies globally and exhibits a complex interplay with tuberculosis (TB). These conditions share several pathogenic pathways, notably involving apoptosis and autophagy, which play critical roles in disease progression and therapeutic responsiveness. MicroRNAs (miRNAs) function as pivotal post-transcriptional regulators, with miR-34a and miR-182 increasingly recognized as key modulators. Beyond their established roles in tumor development and host-pathogen interactions, these miRNAs influence diagnostic accuracy and therapeutic approaches in both lung cancer and TB Methods To investigate miRNA-driven regulatory mechanisms, A549 lung adenocarcinoma cells and THP-1 monocytic cells were transfected with vectors designed to overexpress miR-34a and miR-182. Apoptotic and autophagic processes were quantitatively assessed using high-resolution flow cytometry alongside functional validation assays. Additionally, the expression of key apoptotic and autophagy-related genes was analyzed to characterize downstream molecular effects resulting from miRNA modulation. Results Quantitative real-time PCR analysis demonstrated that miR-34a upregulated Bax while downregulating Bcl-2, leading to a pronounced increase in the Bax/Bcl-2 ratio. In contrast, miR-182 enhanced the expression of both Bax and Bcl-2, yet still facilitated apoptosis through an overall elevation of the Bax/Bcl-2 ratio. Within the autophagy-related signaling network, miR-34a exerted a suppressive effect on IL6, FOXO3, and TNFα expression, whereas miR-182 promoted the expression of genes associated with autophagic activity. These molecular findings were corroborated by flow cytometry, which revealed increased apoptotic activity accompanied by diminished autophagy. Collectively, the data indicate distinct yet complementary regulatory functions of miR-34a and miR-182 in determining cellular fate. Conclusions miR-34a and miR-182 exert significant regulatory effects on apoptotic and autophagic pathways in the context of lung cancer and tuberculosis. Their differentiated but coordinated actions highlight their potential utility as diagnostic biomarkers and therapeutic modulators. These findings suggest promising translational implications for the precision management of both infectious and malignant pulmonary disorders.

MiR-182 and MiR-34a regulate autophagy and apoptosis in tuberculosis and lung cancer

期刊论文
发表日期：

2026年2月25日

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Leila Alimardanian,
Bahram M. Soltani,
Shiva Irani,
Mojgan Sheikhpour

摘要

Background

Lung cancer continues to be among the most fatal malignancies globally and exhibits a complex interplay with tuberculosis (TB). These conditions share several pathogenic pathways, notably involving apoptosis and autophagy, which play critical roles in disease progression and therapeutic responsiveness. MicroRNAs (miRNAs) function as pivotal post-transcriptional regulators, with miR-34a and miR-182 increasingly recognized as key modulators. Beyond their established roles in tumor development and host-pathogen interactions, these miRNAs influence diagnostic accuracy and therapeutic approaches in both lung cancer and TB

Methods

To investigate miRNA-driven regulatory mechanisms, A549 lung adenocarcinoma cells and THP-1 monocytic cells were transfected with vectors designed to overexpress miR-34a and miR-182. Apoptotic and autophagic processes were quantitatively assessed using high-resolution flow cytometry alongside functional validation assays. Additionally, the expression of key apoptotic and autophagy-related genes was analyzed to characterize downstream molecular effects resulting from miRNA modulation.

Results

Quantitative real-time PCR analysis demonstrated that miR-34a upregulated Bax while downregulating Bcl-2, leading to a pronounced increase in the Bax/Bcl-2 ratio. In contrast, miR-182 enhanced the expression of both Bax and Bcl-2, yet still facilitated apoptosis through an overall elevation of the Bax/Bcl-2 ratio. Within the autophagy-related signaling network, miR-34a exerted a suppressive effect on IL6, FOXO3, and TNFα expression, whereas miR-182 promoted the expression of genes associated with autophagic activity. These molecular findings were corroborated by flow cytometry, which revealed increased apoptotic activity accompanied by diminished autophagy. Collectively, the data indicate distinct yet complementary regulatory functions of miR-34a and miR-182 in determining cellular fate.

Conclusions

miR-34a and miR-182 exert significant regulatory effects on apoptotic and autophagic pathways in the context of lung cancer and tuberculosis. Their differentiated but coordinated actions highlight their potential utility as diagnostic biomarkers and therapeutic modulators. These findings suggest promising translational implications for the precision management of both infectious and malignant pulmonary disorders.