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

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.

Myricitrin inhibits fibroblast-like synoviocyte-mediated rheumatoid synovial inflammation and joint destruction by targeting AIM2

“…Previous studies have shown that Myr exerts anti-inflammatory effects by inhibiting the activation of AKT ( Schwanke et al, 2013 ). In addition, AIM2 was also reported to regulate the activation of PI3K/AKT in other cell lines ( Zheng et al, 2022 ). Thus, we investigated whether AIM2 modulates RA FLS functions by regulating AKT activation.…”

“…It was reported that oral administration of Myr inhibited dextran sulfate sodium (DSS)-induced experimental colitis in mice by regulating the activation of AKT ( Schwanke et al, 2013 ). In addition, AIM2 also showed an inhibitory effect on the proliferation, invasion, and migration of osteosarcoma cells by reducing AKT phosphorylation ( Zheng et al, 2022 ). Thus, we further explored whether AIM2 mediates the Myr-induced inhibitory effect on abnormal RA FLS functions by regulating the PI3K/AKT signaling pathway.…”

Development and validation of apoptosis‐related signature and molecular subtype to improve prognosis prediction in osteosarcoma patients

“…Recently, research reports have indicated that dysregulation of ARGs plays a critical role in the incidence and progression of various cancers by disrupting the balance between cell division and cell death, 29–31 including osteosarcoma 32–34 . For the purpose of smoothly conducting the present research, we used the GEO and TARGET datasets to obtain information on the expression of ARGs and osteosarcoma patients.…”

“…6,28 The most effective method of improving the prognosis of these patients is to identify patients at high risk in a timely manner and to implement more and cell death, [29][30][31] including osteosarcoma. [32][33][34] For the purpose of smoothly conducting the present research, we used the GEO and TARGET datasets to obtain information on the expression of ARGs and osteosarcoma patients. By conducting consensus clustering analysis, we identified two apoptosis-related molecular subtypes based on ARGs, named Cluster 1 and Cluster 2, and both PCA and tSNE plotters based on ARG expression showed a clear distinction between the two clusters.…”

AIM2 and Psoriasis

“…Indeed, Wnt5a increases keratinocyte proliferation by secreting TNF-a, IL-12, and IL-23 but repressing the Notch1 pathways which could activate the AIM2 inflammasome (168,169). In contrast, AIM2 might repress proliferation by inactivating the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway in osteosarcoma cells (170). Wilson et al shown that AIM2 inhibits tumor cell proliferation by suppressing AKT phosphorylation in colonic epithelial cells and colon cancer cells, does not affect body inflammation and inflammasomes activation (171).…”