MicroRNA-126 inhibits colon cancer cell proliferation and invasion by targeting the chemokine (C-X-C motif) receptor 4 and Ras homolog gene family, member A, signaling pathway

Abstract

MicroRNA-126 (miR-126) suppresses the migration, proliferation and invasion of colon cancer cells. However, the underlying mechanisms of miR-126 in colon cancer have not been fully elucidated. In this study, in vivo experiments revealed that miR-126 inhibits colon cancer growth and metastasis. Furthermore, miR-126 was down-regulated in human colon cancer tissue, and its expression was inversely correlated with TNM stage and metastasis of patients. Low level of miR-126 identified patients with poor prognosis. And we found that miR-126 expression was negatively correlated with the expression levels of chemokine (C-X-C motif) receptor 4 (CXCR4) and components of signaling pathway of Ras homolog gene family, member A (RhoA) in vitro and in vivo. Moreover, we verified that miR-126 negatively regulated CXCR4 and RhoA signaling in vitro. In addition, either in miR-126-overexpressing or in miR- 126-silenced colon cancer cells, the restoration of CXCR4 could significantly reverse the proliferation and invasion, as well as abolish the effects of miR-126 on RhoA signaling pathway. Collectively, these results demonstrated that miR-126 acts as a tumor suppressor by inactivating RhoA signaling via CXCR4 in colon cancer. And miR-126 may serve as a prognostic marker for monitoring and treating colon cancer.

RETRACTED: lncRNA HOTAIR promotes gastric cancer proliferation and metastasis via targeting miR‐126 to active CXCR4 and RhoA signaling pathway

“…Previous studies reported the tumor suppressor role of miR‐126 in colon cancer by negatively regulating SDF‐1/CXCR4 and RhoA signaling .Thus, we examined downstream proteins of both pathways in gastric cancer cells. Real‐time PCR results observed a significant increase in CXCR4 and RhoGEF, a critical protein in RhoA activation, and downregulation of ARHGAP5 at the mRNA level in HOTAIR knockdownedBGC‐823 cells (Fig.…”

Prognostic value of microRNAs in colorectal cancer: a meta-analysis

“…Two studies 14 , 19 focused on associations between high blood miR141 levels and OS, indicating that CRC patients with high blood miR141 levels had significantly shorter OS than those with low miR141 expression (HR 2.52, 95% CI 1.68–3.77, P <0.01; Figure 2 ). Five papers 120 , 122 – 125 stressed connections between low tissue miR126 levels and OS, suggesting that CRC patients with low expression of tissue miR126 levels had significantly poorer OS than those with high miR126 expression (HR 1.55, 95% CI 1.24–1.93, P <0.01; Figure 6 ).…”

Folic acid modulates cancer‐associated micro RNAs and inflammatory mediators in neoplastic and non‐neoplastic colonic cells in a different way

“…Interestingly, the ectopic expression of miRNAs miR‐1, miR‐126, miR‐139 as well as the miR‐146a reduced also migratory abilities of cancer cells by targeting the expression of the chemotactic chemokine receptor CXCR4 . This receptor was dose‐dependently up‐regulated by FA in the malignant cells in our study.…”

“…). The repression of these miRNAs suggest a specific growth promoting overall effect of FA on the malignant cells in our study, because ectopic expression of miR‐1, miR‐126, miR‐139 and miR‐34a was shown to suppress the proliferation of colon and other cancer cells . Furthermore, the ectopic expression of miR‐143 restores the responsiveness of colon cancer cells for the anti‐EGFR antibody cetuximab, which is therapeutically used as anti‐cancer drug .…”