AUTHOR=Liu Yun , Su Chao-Yue , Yan Yan-Yan , Wang Jian , Li Jia-Jun , Fu Ji-Jun , Wang Yu-Qing , Zhang Jian-Ye 

TITLE=Exosomes of A549 Cells Induced Migration, Invasion, and EMT of BEAS-2B Cells Related to let-7c-5p and miR-181b-5p

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.926769

DOI=10.3389/fendo.2022.926769

ISSN=1664-2392

ABSTRACT=As carriers containing abundant biological information, exosomes could deliver the property of donor cells to recipient cells. Emerging researches have shown that tumor cells could secrete a mass of exosomes into microenvironment to regulate the bystander cells. However, the underlying mechanisms of such a phenomenon remain largely unexplored. In this research, we purified and identified the exosomes of A549 cells, and found that A549 cells-derived exosomes promote BEAS-2B cells migration, invasion and EMT. Importantly, we observed that let-7c-5p and miR-181b-5p were attenuated in A549 cells-derived exosomes compared to BEAS-2B cells-derived exosomes. The analysis of miRNAs expression level in BEAS-2B cells indicated that incubation with A549 cells-derived exosomes reduced the expression levels of let-7c-5p and miR-181b-5p. In transient transfections assay, we found that down-regulation of let-7c-5p and miR-181b-5p simultaneously shown stronger promotion of BEAS-2B cells migration and invasion than individually. Moreover, exosomes secreted from A549 cells with up-regulated expression of let-7c-5p and miR-181b-5p significantly reduce their regulatory effect on BEAS-2B cells. Bioinformatics analyses revealed that let-7c-5p and miR-181b-5p inhibit the EMT process mainly by regulating focal adhesion and MAPK signaling pathway. Thus, our data demonstrated that A549 cells-derived exosomal let-7c-5p and miR-181b-5p could induce migration, invasion and EMT in BEAS-2B cells, which might be regulated through focal adhesion and MAPK signaling pathway. The expression level of let-7c-5p and miR-181b-5p may show great significance for the early diagnosis of lung cancer.