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.