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TGF-?-mediated exosomal lnc-MMP2-2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression.


ABSTRACT: Previous studies indicated that transforming growth factor (TGF)-?-mediated exosomal microRNAs (miRNAs) regulate the migration and invasion of lung cancer cells; however, whether and how TGF-?-mediated exosomal long noncoding (lnc) RNAs regulate migration and invasion of lung cancer cells remains unclear. Here, coculture experiments showed that TGF-? pretreatment increased the migration and invasion potential of lung cancer cells and TGF-? pretreated A549 cells increases vascular permeability. Furthermore, we found that TGF-?-mediated exosomes, as carriers of intercellular communication, regulated lung cancer invasion, and vascular permeability. Transcriptional analysis also revealed that lnc-MMP2-2 was highly enriched in TGF-?-mediated exosomes and might function by increasing the expression of matrix metalloproteinase (MMP)2 through its enhancer activity, with ectopic expression and silencing of lnc-MMP2-2 affecting lung cancer invasion and vascular permeability. Additionally, lnc-MMP2-2 and MMP2 expression was assessed semiquantitatively, and tissue-specific correlations between lnc-MMP2-2 and MMP2 expression were evaluated. These results suggested that exosomal lnc-MMP2-2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer.

SUBMITTER: Wu DM 

PROVIDER: S-EPMC6198203 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

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