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

Li,Rongrui; Liu,Shichen; Li,Yao; Tang,Qingxi; Xie,Yunchuan; Zhai,Raosheng

doi:10.3892/mmr.2018.9131

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

Authors:
- Rongrui Li
- Shichen Liu
- Yao Li
- Qingxi Tang
- Yunchuan Xie
- Raosheng Zhai
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Affiliations: Second Department of Orthopaedic Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China, First Department of Orthopaedic Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China, Department of Emergency Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China
Published online on: June 5, 2018 https://doi.org/10.3892/mmr.2018.9131
Pages: 1616-1622
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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/β‑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/β‑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‑β‑catenin axis played an important role in OS progression.

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