Conclusion
miR-5703 operates as an oncogenic factor in lung cancer. After being taken up by TAECs, exosomal miR-5703 promotes angiogenesis, EndMT, and barrier damage by targeting ING4. Hence, miR-5703 is a potential target in the lung cancer microenvironment.
Material and methods
We analyzed Gene Expression Omnibus datasets and performed quantitative real-time polymerase chain reaction to determine miR-5703 expression levels in lung cancer tissues. Exosomes derived from lung cancer cells were identified, and the effects of miR-5703 inhibitors or mimics on malignant biological behavior were evaluated in the lung cancer cells. Moreover, to understand these effects on TAECs, we assessed angiogenesis, endothelial-mesenchymal transition (EndMT), and barrier function after treatment with miR- 5703 inhibitors or the exosome-assimilated inhibitor cytochalasin D. Tumor-bearing mouse models were used in validating the tumor-promoting effects of exosomes derived from lung cancer cells, and the markers of angiogenesis, EndMT, and barrier function were examined.
Methods
We analyzed Gene Expression Omnibus datasets and performed quantitative real-time polymerase chain reaction to determine miR-5703 expression levels in lung cancer tissues. Exosomes derived from lung cancer cells were identified, and the effects of miR-5703 inhibitors or mimics on malignant biological behavior were evaluated in the lung cancer cells. Moreover, to understand these effects on TAECs, we assessed angiogenesis, endothelial-mesenchymal transition (EndMT), and barrier function after treatment with miR- 5703 inhibitors or the exosome-assimilated inhibitor cytochalasin D. Tumor-bearing mouse models were used in validating the tumor-promoting effects of exosomes derived from lung cancer cells, and the markers of angiogenesis, EndMT, and barrier function were examined.
Objective
Lung cancer, as a prevalent malignancy, continues to be a considerable clinical challenge. This study aimed to elucidate the role of microRNA-5703 (miR-5703) in lung cancer progression and to assess the effect of exosomal miR-5703 on tumor-associated endothelial cells (TAECs). Material and
Results
Our results showed that miR-5703 was up-regulated in the lung cancer cells and patient-derived exosomes. miR-5703 facilitated cell growth, migration, invasion, in LC cells, and impaired the barrier function, which promoted angiogenesis and EndMT of TAECs by carrying in exosomes through targeting inhibitor of growth family member 4 (ING4) was identified as target of miR-5703 (P < 0.05). In vivo, the tumor-promoting effects of lung cancer cell-derived exosomes were rescued by miR-5703 inhibitors, leading to the up-regulation of ING4 expression and reduction in vascular distribution in the tumor tissues (P < 0.05).