Song Jianping, Shu Hongchun, Zhang Ling, Xiong Jianping
Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Oncology, The Third Affiliated Hospital of Nanchang University, Nanchang, China.
J Cell Biochem. 2019 May;120(5):6937-6951. doi: 10.1002/jcb.27743. Epub 2019 Jan 22.
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.
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.
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.
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.
血管生成在结直肠癌（CRC）的发生和发展中起关键作用。在本研究中，我们调查了长链非编码RNA（lncRNA）GAS5对CRC血管生成、侵袭和转移的影响，以及Wnt/β-连环蛋白信号通路的参与情况。
收集52例CRC患者的CRC组织和癌旁正常组织。通过实时定量聚合酶链反应（RT-qPCR）在体内和体外测定GAS5表达。然后用RT-qPCR和蛋白质印迹法鉴定Wnt/β-连环蛋白信号通路关键基因的表达。选择GAS5表达最低的CRC细胞，分别转染si-GAS5、oe-GAS5或XAV939，以验证GAS5和Wnt/β-连环蛋白信号通路对CRC细胞活性的影响。检测GAS5对Wnt/β-连环蛋白信号通路激活的影响。观察裸鼠皮下肿瘤生长和微血管密度，并在尾静脉注射CRC细胞后观察体内转移情况。
最初，在CRC组织和细胞中观察到GAS5表达较低。上调GAS5可抑制CRC细胞体外侵袭和迁移，以及体内皮下肿瘤生长、血管生成和肝转移。此外，在CRC组织和细胞中检测到Wnt/β-连环蛋白信号通路被激活，而GAS5可抑制其激活。Wnt/β-连环蛋白信号通路促进CRC细胞体外侵袭和迁移、体内皮下肿瘤生长、血管生成和肝转移。
综上所述，研究结果表明lncRNA GAS5抑制Wnt/β-连环蛋白信号通路的激活，从而抑制CRC的血管生成、侵袭和转移。
