Preprint Article Version 1 This version is not peer-reviewed

Tuberculous Pleural Effusion-Derived Exosomal miR-130-3p and miR-423-5p Promote the Proliferation of Lung Cancer Cells via Cyclin D1

Version 1 : Received: 15 August 2024 / Approved: 15 August 2024 / Online: 16 August 2024 (04:44:49 CEST)

How to cite: Kang, H.-J.; Yun, S.; Shin, S.-H.; Youn, D. H.; Son, G.-H.; Lee, J. J.; Hong, J. Y. Tuberculous Pleural Effusion-Derived Exosomal miR-130-3p and miR-423-5p Promote the Proliferation of Lung Cancer Cells via Cyclin D1. Preprints 2024, 2024081198. https://doi.org/10.20944/preprints202408.1198.v1 Kang, H.-J.; Yun, S.; Shin, S.-H.; Youn, D. H.; Son, G.-H.; Lee, J. J.; Hong, J. Y. Tuberculous Pleural Effusion-Derived Exosomal miR-130-3p and miR-423-5p Promote the Proliferation of Lung Cancer Cells via Cyclin D1. Preprints 2024, 2024081198. https://doi.org/10.20944/preprints202408.1198.v1

Abstract

Epidemiologic studies have shown an association between tuberculosis and lung cancer. The al-tered tumor microenvironment after tuberculosis infection appears to contribute to cancer pro-gression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of select exosomal microRNAs. TPE-derived exosome treatment en-hanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell inva-sion. Exosome-mediated transfer of select microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phos-phorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p sup-pressed the promotion of lung cancer by TPE derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TBE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer.

Keywords

tuberculosis; lung cancer; exosome; intercellular communication

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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