Long noncoding RNA GAS5 inhibits angiogenesis and metastasis of colorectal cancer through the Wnt/β-catenin signaling pathway.

OBJECTIVE: Angiogenesis plays a key role in the tumorigenesis and progression of colorectal cancer (CRC). In this study, we investigated the effect of long noncoding RNA (lncRNA) GAS5 on the angiogenesis, invasion, and metastasis of CRC, and the involvement of the Wnt/β-catenin signaling pathway.

METHODS: CRC tissues and adjacent normal tissues were collected from 52 patients with CRC. GAS5 expression was determined in vivo and in vitro by real-time quantitative polymerase chain reaction (RT-qPCR). Then RT-qPCR and Western blot were used to identify expression of key genes of Wnt/β-catenin signaling pathway. CRC cells with lowest GAS5 expression were selected and subjected to si-GAS5, oe-GAS5, or XAV939 to validate the effect of GAS5 and Wnt/β-catenin signaling pathway on CRC cell activities. The activation of Wnt/β-catenin signaling pathway was determined in response to GAS5. Subcutaneous tumor growth and microvascular density were observed in nude mice, in which in vivo metastasis was observed following tail vein injection of CRC cells.

RESULTS: Initially, poor expression of GAS5 was observed in CRC tissues and cells. Upregulated GAS5 repressed CRC cell invasion and migration in vitro, as well as subcutaneous tumor growth, angiogenesis, and liver metastases in vivo. Furthermore, the Wnt/β-catenin signaling pathway was determined to be activated in CRC tissues and cells, while its activation was inhibited by GAS5. The Wnt/β-catenin signaling pathway promoted the CRC cell invasion and migration in vitro, subcutaneous tumor growth, angiogenesis and, liver metastases in vivo.

CONCLUSION: Taken together, the results of the study conclude that lncRNA GAS5 inhibited the activation of the Wnt/β-catenin signaling pathway, thereby suppressing the angiogenesis, invasion, and metastasis of CRC.