miR-622 inhibits angiogenesis by suppressing the CXCR4–VEGFA axis in colorectal cancer

Angiogenesis is essential for tumor metastasis. Our previous study has revealed that miR-622 inhibits colorectal cancer (CRC) metastasis. Here, we aimed to explore the effects and potential molecular mechanisms of action of miR-622 on angiogenesis. We found that overexpression of miR-622 inhibited CRC angiogenesis in vitro, according to suppression of proliferation, migration, tube formation, and invasiveness of human umbilical vein endothelial cells (HUVECs) treated with a tumor cell–conditioned medium derived from Caco-2 or HT-29 cells. Likewise, enhanced miR-622 expression suppressed CRC angiogenesis in vivo as determined by the measurement of Ki67 and VEGFA levels and microvessel density (by immunostaining). CXCR4, encoding a positive regulator of vascular endothelial growth factor A (VEGFA), was shown to be a direct target of miR-622. Overexpression of CXCR4 attenuated the inhibition of VEGFA expression by miR-622 and reversed the loss of tumor angiogenesis caused by miR-622. Taken together, these data show that miR-622 inhibits CRC angiogenesis by suppressing the CXCR4–VEGFA signaling axis, which represents a promising target for developing a new therapeutic strategy against CRC. •miR-622 can inhibit proliferation, capillary tube formation, and migration of HUVECs.•miR-622 suppresses tumor growth and angiogenesis in vivo.•CXCR4 is a direct target of miR-622.•miR-622 inhibits angiogenesis by suppressing the CXCR4–VEGFA axis.