# miR-200-mediated inactivation of cancer-associated fibroblasts via targeting of NRP2-VEGFR signaling attenuates lung cancer invasion and metastasis

## TL;DR

This study shows that miR-200 can stop cancer-associated fibroblasts from helping lung cancer spread by targeting NRP2-VEGFR signaling.

## Contribution

The novel finding is that miR-200 inhibits CAF activity via NRP2-VEGFR signaling, offering new therapeutic targets for lung cancer.

## Key findings

- miR-200 prevents CAFs from promoting lung cancer cell migration and metastasis.
- NRP2 is a key target of miR-200 in CAFs, mediating its anti-cancer effects.
- miR-200 reduces CAF interactions with macrophages and endothelial cells.

## Abstract

Cancer-associated fibroblasts (CAFs) play a substantial role in promoting cancer cell motility, drug resistance, angiogenesis, and metastasis; therefore, extensive research has been conducted to determine their mode of activation. We aimed to identify whether miRNA-200 (miR-200), a widely recognized suppressor of epithelial-mesenchymal transition, prevents CAFs from promoting cancer progression. Overexpression of miR-200 prevented CAFs from promoting lung cancer cell migration, invasion, tumorigenicity, and metastasis. Additionally, miR-200 suppressed the ability of CAFs to recruit and polarize macrophages toward the M2 phenotype, as well as the migration and tube formation of vascular endothelial cells. NRP2, a co-receptor of vascular endothelial growth factor receptor (VEGFR), was confirmed to be a target of miR-200, which mediates the functional activity of miR-200 in CAFs. NRP2-VEGFR signaling facilitates the secretion of VEGF-D and pleiotrophin from CAFs, leading to the activation of cancer cell migration and invasion. These findings suggest that miR-200 remodels CAFs to impede cancer progression and metastasis and that miR-200 and NRP2 are potential therapeutic targets in the treatment of lung cancer.

Ahn and colleagues demonstrated that the miR-200 family is downregulated in lung CAFs. miR-200 hinders CAF activation via NRP2/VEGFR signaling, limiting cancer cell mobility. miR-200 also reduces CAF interactions with macrophages and endothelial cells, proposing miR-200 and NRP2 as targets for lung cancer treatment and prognosis.