Long noncoding RNA AFAP1-AS1 enhances cell proliferation and invasion in osteosarcoma through regulating miR-4695-5p/TCF4-β-catenin signaling

Long noncoding RNA AFAP1-AS1 has been shown to promote tumor progression in several human cancer types, such as thyroid cancer, tongue squamous cell carcinoma and lung cancer. However, the role of AFAP1-AS1 in osteosarcoma (OS) has not been investigated. In the present study, the expression of AFAP1-AS1 was significantly upregulated in OS tissues and cell lines. Moreover, AFAP1-AS1 expression was negatively correlated with OS patient prognosis. Besides, AFAP1-AS1 knockdown significantly inhibited the proliferation and invasion of OS cells in vitro. Furthermore, in vivo xenograft experiments indicated that AFAP1-AS1 depletion delayed tumor growth. Regarding the underlying mechanism, AFAP1-AS1 served as a sponge to repress the level of microRNA (miR)-4695-5p, which targeted transcription factor (TCF)4, a pivot effector of Wnt/-catenin signaling pathway. It was demonstrated that overexpression of AFAP1-AS1 inhibited the expression of miR-4695-5p, while miR-4695-5p overexpression decreased TCF4 expression and reduced activation of Wnt/-catenin pathway. Through rescue assays, it was demonstrated that restoration of TCF4 expression reversed the effects of AFAP1-AS1 knockdown or miR-4695-5p overexpression on OS cells. Taken together, these findings demonstrated that the AFAP1-AS1/miR-4695-5p/TCF4--catenin axis played an important role in OS progression.