LncRNA CRNDE Promote Osteosarcoma Proliferation,Invasion And Epithelial-mesenchymal Transition Via Wnt/β-catenin Signaling Pathway

Backgrounds: Long non-coding RNAs(lncRNAs)play an important role in the development and progression of cancer via regulating cell proliferation,apoptosis,invasion and metastatic pathways.CRNDE(colorectal neoplasia differentially expressed),an lncRNA,functions as an oncogene in some malignant neoplasias,but its role and molecular mechanisms in the progression of osteosarcoma(OS)are still poorly understood.Objectives: 1.The expression of CRNDE in osteosarcoma cell lines and tissues 2.The regulatiuon mechanism of CRNDE expression 3.The role and mechanism of CRNDE in osteosarcoma development Methods: In the present study,quantitative real-time polymerase chain reaction(RT-PCR)was used to evaluate the expression of CRNDE in osteosarcoma tissues and cell lines(U2OS,MG63,MNNG/HOS,and Saos-2)compared with that in the adjacent tissues/normal osteoblast cells(hFOB1.19).The role of CRNDE in OS lines were assessed using CCK-8,colony formation,EDU staining,Tunel staining,flow cytometry,Transwell assays and western blot,respectively.Results: The results showed that CRNDE was expressed highly in OS tissues and cell lines,and was partly induced by SP1.CRNDE knockdown inhibited OS cell proliferation and invasion,and induced G0/G1 arrest and apoptosis.In vivo assays also confirmed the ability of CRNDE to promote tumor growth.Moreover,CRNDE knockdown reduced the expression of mesenchymal markers N-cadherin,vimentin and snail,and increased the expression of epithelial markers E-cadherin and ZO-1.The mechanistic investigations showed that CRNDE promoted glycogen synthase kinase-3β phosphorylation to activate Wnt/β-catenin pathway.Conclusion: These findings suggested that lncRNA CRNDE acts as an oncogene in promoting OS proliferation,invasion,and epithelial-mesenchymal transition,and might be a promising therapeutic target for OS.