Suppression of antitumor cytokine IL‑24 by PRG4 and PAI‑1 may promote myxoid liposarcoma cell survival

Oikawa,Kosuke; Kuroda,Masahiko; Ehata,Shogo

doi:10.3892/br.2023.1642

Suppression of antitumor cytokine IL‑24 by PRG4 and PAI‑1 may promote myxoid liposarcoma cell survival

Authors:
- Kosuke Oikawa
- Masahiko Kuroda
- Shogo Ehata
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Affiliations: Department of Pathology, School of Medicine, Wakayama Medical University, Wakayama 641‑8509, Japan, Department of Molecular Pathology, Tokyo Medical University, Tokyo 160‑8402, Japan
Published online on: July 26, 2023 https://doi.org/10.3892/br.2023.1642
Article Number: 60

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Abstract

Suppression of the antitumor cytokine interleukin‑24 (IL‑24) is critical for the survival of myxoid liposarcoma (MLS) cells. It has been previously demonstrated by the authors that an MLS‑specific chimeric oncoprotein, translocated in liposarcoma‑CCAAT/enhancer‑binding protein homologous protein (TLS‑CHOP), supresses IL24 mRNA expression via induction of proteoglycan 4 (PRG4) to sustain MLS cell proliferation. However, IL‑24 has also been revealed to be suppressed by the ubiquitin‑proteasome system in human ovarian and lung cancer cells. Therefore, the aim of the present study was to elucidate the mechanism of IL‑24 suppression in MLS cells. The results revealed that the proteasome inhibitor, MG‑132, induced cell death in MLS cells in vitro; this effect was reduced following IL‑24 knockdown. This indicated that proteasomal degradation of IL‑24 may be an important process for MLS cell survival. In addition, it was also previously revealed by the authors that knockdown of plasminogen activator inhibitor‑1 (PAI‑1), a TLS‑CHOP downstream molecule, suppressed the growth of MLS cells, thus instigating the investigation of the effect of PAI‑1 on IL‑24 expression in MLS cells. Double knockdown of PAI‑1 and IL‑24 negated the growth‑suppressive effect of PAI‑1 single knockdown in MLS cells. Interestingly, PAI‑1 single knockdown did not increase the mRNA expression of IL24, but it did increase the protein abundance of IL‑24, indicating that PAI‑1 suppressed IL‑24 expression by promoting its proteasomal degradation. Moreover, treatment of MLS cells with a PAI‑1 inhibitor, TM5275, induced IL‑24 protein expression and apoptosis. Collectively, the results of the present as well as previous studies indicated that IL‑24 expression may be suppressed at the transcriptional level by PRG4 and at the protein level by PAI‑1 in MLS cells. Accordingly, PAI‑1 may represent an effective therapeutic target for MLS treatment.

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