混合型脂肪肉瘤（MLS）细胞的存活关乎抗肿瘤细胞因子白介素-24（IL-24）的抑制。作者先前研究表明，特异性于MLS的混合型肉瘤融合蛋白转位于脂肪肉瘤-CCAAT/enhancer结合蛋白同源物（TLS-CHOP）通过诱导蛋白聚糖4（PRG4）来抑制IL24 mRNA表达，从而维持MLS细胞的增殖。然而，IL-24在人类卵巢癌和肺癌细胞中也被泛素-蛋白酶体系统抑制。因此，本研究的目的是阐明MLS细胞中IL-24抑制的机制。结果显示，蛋白酶体抑制剂MG-132在体外诱导MLS细胞死亡；在IL-24沉默后，这种效应减弱，表明IL-24的蛋白酶体降解可能是MLS细胞存活的重要过程。另外，作者还先前研究显示抑制副溶血酶原激活物抑制因子-1（PAI-1），即TLS-CHOP下游分子，抑制了MLS细胞的生长，因此展开了研究PAI-1对MLS细胞中IL-24表达的影响。双重沉默PAI-1和IL-24取消了单一PAI-1沉默对MLS细胞的生长抑制效应。有趣的是，PAI-1单一沉默并未增加IL24的mRNA表达，但却增加了IL-24蛋白的丰度，表明PAI-1通过促进其蛋白酶体降解来抑制IL-24的表达。此外，使用PAI-1抑制剂TM5275处理MLS细胞，诱导了IL-24蛋白的表达和细胞凋亡。综上，本研究及先前研究结果表明，在MLS细胞中，PRG4可能通过转录水平抑制IL-24的表达，而PAI-1可能通过蛋白水平抑制IL-24的表达。因此，PAI-1可能是MLS治疗的有效靶点。版权所有 ©2020, Spandidos出版社。

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.Copyright © 2020, Spandidos Publications.