AIM2 inhibits the proliferation, invasion and migration, and promotes the apoptosis of osteosarcoma cells by inactivating the PI3K/AKT/mTOR signaling pathway

Zheng,Jianping; Liu,Changhao; Shi,Jiandang; Wen,Kun; Wang,Xiangxin

doi:10.3892/mmr.2021.12569

AIM2 inhibits the proliferation, invasion and migration, and promotes the apoptosis of osteosarcoma cells by inactivating the PI3K/AKT/mTOR signaling pathway

Authors:
- Jianping Zheng
- Changhao Liu
- Jiandang Shi
- Kun Wen
- Xiangxin Wang
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Affiliations: Department of Orthopedic Traumatology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China, Department of Orthopedics, Zhangye People's Hospital Affiliated to Hexi University, Zhangye, Gansu 734000, P.R. China, Department of Spine Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China, Department of Orthopedics, Ningxia Gemflower Hospital, Yinchuan, Ningxia Hui Autonomous Region 750006, P.R. China, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750001, P.R. China
Published online on: December 14, 2021 https://doi.org/10.3892/mmr.2021.12569
Article Number: 53
Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma is a primary bone tumor that mainly occurs in children and adolescents. Absent in melanoma 2 (AIM2) has been demonstrated to be involved in regulating the occurrence and development of cancer, exerting oncogenic and pro‑cancer effects; however, its role in osteosarcoma is poorly understood. The present study aimed to explore the function and molecular mechanism of AIM2 in the progression of osteosarcoma. In the present study, AIM2 expression was predicted using the Cancer Cell Line Encyclopedia database and examined in several osteosarcoma cell lines using reverse transcription‑quantitative PCR and western blotting. Following AIM2 overexpression, cell proliferation and apoptosis were examined using Cell Counting Kit‑8, colony formation and TUNEL staining assays. The expression levels of proteins related to apoptosis, epithelial‑mesenchymal transition (EMT) and the PI3K/AKT/mTOR signaling pathway were determined by western blotting. Additionally, cell invasion and migration were assessed using Transwell and wound healing assays. After addition of the PI3K/AKT/mTOR signaling pathway inhibitor LY294002 or activator 740Y‑P, cell function analysis was performed. The results demonstrated that AIM2 was expressed at low levels in osteosarcoma cell lines. AIM2 overexpression inhibited proliferation, invasion, migration and EMT, and promoted apoptosis in osteosarcoma cells. Furthermore, the levels of phosphorylated (p)‑PI3K, p‑AKT and p‑mTOR were markedly downregulated following AIM2 overexpression. Furthermore, LY294002 treatment had the same effects as AIM2 upregulation on osteosarcoma cell proliferation, apoptosis, invasion, migration and EMT. By contrast, 740Y‑P reversed the effects of AIM2 overexpression on the behavior of osteosarcoma cells. Overall, the findings of the present study demonstrated that AIM2 may inhibit the progression of osteosarcoma by inactivating the PI3K/AKT/mTOR signaling pathway, and suggested that AIM2 may be a promising marker for the treatment of osteosarcoma.

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