MiR-19b-3p facilitates colorectal cancer metastasis by mediating the crosstalk between tumor-associated endothelial cells and malignant cells

Background The crosstalk between tumor cells and stromal components in the tumor microenvironment critically influences colorectal cancer (CRC) progression and metastasis. The role of tumor-associated endothelial cells (TAECs) in this process is not fully understood. This study aimed to elucidate the function of miR-19b-3p in mediating CRC-endothelial cell communication. Methods The effects of miR-19b-3p were investigated in CRC cells (HCT116) and human umbilical vein endothelial cells (HUVECs) using functional assays and molecular analyses. A co-culture model was employed to study intercellular crosstalk. In vivo validation was performed using a mouse peritoneal tumor model. Circulating miR-19b-3p levels were measured in CRC patient samples and correlated with clinicopathological parameters. Results miR-19b-3p promoted epithelial-to-mesenchymal transition (EMT) in HCT116 cells by suppressing ZMYND11 and activating the MAPK pathway. In HUVECs, it induced endothelial-to-mesenchymal transition (EndMT) via upregulation of SOX9. Co-culture led to reciprocal elevation of miR-19b-3p in both cell types, indicating a reinforcing bidirectional loop. In mice, miR-19b-3p overexpression increased peritoneal tumor burden and induced EMT markers (loss of E-cadherin, gain of N-cadherin). Clinically, elevated circulating miR-19b-3p in CRC patients was associated with advanced disease stage and poor prognosis. Conclusion Our findings reveal that miR-19b-3p orchestrates tumor-endothelial interactions by synchronously promoting EMT and EndMT, thereby driving a pro-metastatic microenvironment. Circulating miR-19b-3p represents a promising biomarker and potential therapeutic target in metastatic colorectal cancer.