Long Noncoding RNA GAS5 Inhibits Angiogenesis,Invasion And Metastasis Of Colorectal Cancer Via The Wnt/β-catenin Signaling Pathway

Background: The incidence of colorectal cancer is the third in tumors,and the fatality rate is the second in tumors,which seriously endangers human health and life safety.The 5-year survival rate of patients with colorectal cancer detected early can reach 80-90% after effective surgical treatment.However,due to the rapid progression of colorectal cancer cells,patients are already in the late stage when detected,with multiple metastases and lost opportunities for surgical treatment,leading to a high mortality rate of patients with colorectal cancer.At present,the only treatment for advanced stage is chemotherapy and radiotherapy.Chemotherapy has poor targeting,toxicity and side effects.Radiotherapy is only for local irradiation,which may be accompanied by local bleeding,radiation-induced lung injury and other complications.Therefore,we urgently need to find new molecular targets with high efficiency,low toxicity and high targeting for colorectal cancer,and develop new strategies for the treatment of colorectal cancer.Long non codingRNAs are not responsible for protein coding,but participate in many physiological and pathological regulation in the form ofRNA at various levels.Long noncodingRNAs play an important role in tumorigenesis and development.Among them,LncRNA GAS5 is low expressed in many tumor tissues and cells,while overexpression of GAS5 can significantly inhibit the proliferation of tumor cells and finally achieve the anti-tumor effect.Objective: Previous studies have shown that LncRNA GAS5 is low expressed in many tumor tissues and cells,suggesting that LncRNA GAS5 is a potential anti-tumor target.The low expression of LncRNA can induce the activation of Wnt/β-catenin signaling pathway,and the activation of Wnt/β-catenin signaling pathway can induce the tumorigenesis and development of tumor.However,whether LncRNA GAS5 can inhibit the proliferation of colorectal cancer cells via regulating Wnt/β-catenin signaling pathway and the molecular mechanism of angiogenesis,invasion and metastasis of colorectal cancer induced by overexpression of LncRNA GAS have not been elucidated.The mRNA and protein expressions of lncRNA GAS5 in colorectal cancer tissues and cells were detected by Q-PCR and Western Blot.The effects of overexpression of lncRNA GAS5 on angiogenesis,invasion and metastasis of colorectal cancer were evaluated in vitro and in vivo.The effects of Wnt/β-catenin signaling pathway on angiogenesis,invasion and metastasis of colorectal cancer were elucidated.The role of LncRNA GAS5 in inducing angiogenesis,invasion and metastasis of colorectal cancer was elucidated.The regulation of lncRNA GAS5 on colorectal cancer angiogenesis,invasion and metastasis was dependent on the Wnt/β-catenin signaling pathway in vitro and in vivo.Results: LncRNA GAS5 is low expressed in colorectal cancer tissues and cells.Overexpression of LncRNA GAS5 can significantly inhibit angiogenesis,invasion and metastasis of colorectal cancer,and ultimately inhibit the proliferation of colorectal cancer cells.In mechanism,Wnt/β-catenin signaling pathway can promote angiogenesis,invasion and metastasis of colorectal cancer.Overexpression of LncRNA GAS5 restrains angiogenesis,invasion and metastasis of colorectal cancer depends on Wnt/β-catenin signaling pathway.Conclusions: Our findings highlight that Wnt/β-catenin signaling pathway mediates LncRNA GAS5 in inhibiting angiogenesis,invasion,metastasis and proliferation of colorectal cancer.We clearly clarify the molecular mechanism of LncRNA GAS5 in inhibiting colorectal cancer,which strongly support the clinical research of anti-colorectal cancer targeting LncRNA GAS5-Wnt/β-catenin signaling pathway.