Tumour‐derived exosomal miR‐3473b promotes lung tumour cell intrapulmonary colonization by activating the nuclear factor‐κB of local fibroblasts

Abstract

Tumour‐derived exosomes have been shown to induce pre‐metastatic niche formation, favoring metastatic colonization of tumour cells, but the underlying molecular mechanism is still not fully understood. In this study, we showed that exosomes derived from the LLC cells could indeed significantly enhance their intrapulmonary colonization. Circulating LLC‐derived exosomes were mainly engulfed by lung fibroblasts and led to the NF‐κB signalling activation. Further studies indicated that the exosomal miR‐3473b was responsible for that by hindering the NFKB inhibitor delta's (NFKBID) function. Blocking miR‐3473b could reverse the exosome‐mediated NF‐κB activation of fibroblasts and decrease intrapulmonary colonization of lung tumour cells. Together, this study demonstrated that the miR‐3473b in exosomes could mediate the interaction of lung tumour cells and local fibroblasts in metastatic sites and, therefore, enhance the metastasis of lung tumour cells.

Inhibiting collagen I production and tumor cell colonization in the lung via miR-29a-3p loading of exosome-/liposome-based nanovesicles

“…2 A). However, our previous study showed that LLC-derived exosomes promoted LLC colonization in the lung 25 . So, LLC-Exo are not an appropriate carrier to deliver miR-29a-3p.…”

“…Tumor-derived exosomes participate in tumor progression and metastasis by communicating with the tumor microenvironment are vital to establishing the pre-metastatic niche (PMN) 18 , 32 , 33 , 34 . Our previous study identified that lung tumor cell-derived exosomes facilitate lung tumor cell colonization in the lung by activating NF- κ B signaling of lung fibroblasts 25 . Similarly, the uptake of breast cancer-derived exosomes by lung fibroblasts promoted their activation and fibronectin secretion, thus contributing to PMN formation and lung metastasis 35 .…”

“…Mice were sacrificed 21 days after LLC-EGFP-Luc injection, and lung metastasis was measured by bioluminescence imaging and HE staining. All animal experiments were performed according to previous publications 25 . All protocols were approved by the Ethics Committee of Zhengzhou University (Ethical Approval Number: 2021-KY-0028).…”

MicroRNA‐3473b regulates the expression of TREM2/ULK1 and inhibits autophagy in inflammatory pathogenesis of Parkinson disease

“…At present, the regulatory role of miRNAs in a variety of diseases has been confirmed. Mir‐3473b is a miRNA involved in the inflammatory response in a variety of diseases (Du et al., 2020; Wang et al., 2018; Wu et al., 2014). The results of the in vivo and in vitro experiments of the present study are the first to confirm the role of mir‐3473b in PD.…”

Exosomes in Lung Cancer: Actors and Heralds of Tumor Development

“…In addition, through the carried molecules, particularly integrins, tumor exosomes can specifically target different organs or tissues and prepare the pre-metastatic niche [102]. Lewis lung carcinoma cell line produces exosomes containing miR-3473b, which once captured by lung fibroblasts cause NF-kB activation and inflammatory cytokines production, enhancing their intrapulmonary colonization [103]. Lung cancer commonly metastasizes to the brain and bone.…”