Abstract
Extracellular vesicles (EVs) released by tumor cells play important roles on the remodeling of the tumor–stromal environment and on promoting tumor metastasis. Our earlier studies revealed that miR-122-5p, a type of small non-coding RNA, was dysregulated in non-small cell lung cancer (NSCLC) cell-derived EVs. In this study, we found that miR-122-5p was selectively sorted and secreted into lung cancer EVs through binding to RNA-binding protein hnRNPA2B1. In addition, we found that hnRNPA2B1 interacted with miR-122-5p through the EXO-motif. The delivering of lung cancer EVs-miR-122-5p promoted the migration of liver cells, which may play roles in establishing a pre-metastatic micro-environment and hepatic metastasis of lung cancer. Importantly, our findings revealed the molecular mechanism that RNA-binding protein controls the selective sorting of tumor-derived EV miR-122-5p, which potentially promotes lung cancer progression.
Highlights
Extracellular vesicles (EVs) are double-membrane-bound vesicles shed from the cell membrane or secreted by the cell, with a diameter of 30 to 1000 nm [1]
These results demonstrated that hnRNPA2B1 promoted the selective sorting of miR-122-5p into A549 EVs
We found that overexpression of hnRNPA2B1 significantly increased the miR-122-5p level in A549 EVs after 24h of transfection, while it had no influence on the miR-122-5p level in A549 cells
Summary
Extracellular vesicles (EVs) are double-membrane-bound vesicles shed from the cell membrane or secreted by the cell, with a diameter of 30 to 1000 nm [1]. Some RNA-binding proteins (RBPs) have been found to play vital roles on the selective sorting of miRNAs into EVs. For example, a recent study has demonstrated that hnRNPA1 plays an important role in specific packaging of miR-196a into CAF-derived exosomes by binding to a specific motif (UAGGUA) existing at the 5 end of miR-196a, which plays an active role in HNC progression and chemoresistance [15]. We demonstrated that the selective sorting and secretion of tumor suppressor miR-122-5p into lung cancer EVs was regulated by RNA-binding protein hnRNPA2B1. Our studies demonstrated that lung cancer cell-derived EVs promoted the migration of liver cells through delivering miR-122-5p, which might play roles in pre-metastasis micro-environment establishment and potentially influence hepatic metastasis of lung cancer
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