Yu Mingwei, Zhao Huishan, Sun Yujie
Department of Orthopedics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Reproductive Medicine Center, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Front Endocrinol (Lausanne). 2025 Jun 17;16:1591390. doi: 10.3389/fendo.2025.1591390. eCollection 2025.
DEP domain containing 1 (DEPDC1) has been well-known as a significant contributor to tumorigenesis and cancer progression. However, its potential oncogenic mechanism in liposarcoma is still unclear.
In this study, the expression and clinical relevance of DEPDC1 in sarcoma was assessed by employing data from The Cancer Genome Atlas (TCGA) data and conducting Kaplan-Meier online analyses, respectively. Furthermore, the impact of DEPDC1 on cellular functions of liposarcoma cell lines and its underlying mechanisms were studied using the assays.
Here, our findings revealed that the expression levels of DEPDC1 and KIF20A were elevated in liposarcoma compared to the paired adjacent adipose tissues, with their expression positively correlating with the malignancy of liposarcoma. Moreover, patients with high DEPDC1 or KIF20A mRNA levels experienced shorter survival times. assays showed that DEPDC1 overexpression enhanced cell proliferation, migration, and invasion in 93T449 cells, whilst an opposite effect was observed in SW872 cells with DEPDC1 knockdown. Furthermore, potential interacting proteins of DEPDC1 were predicted by STRING, and the DEPDC1-KIF20A interaction was confirmed by co-immunoprecipitation in liposarcoma cells. The deletion of KIF20A partially mitigated the promoting effect of DEPDC1 on the malignant phenotype of liposarcoma cells and the activation of PI3K/AKT/mTOR signaling pathway.
In conclusion, this study suggested that DEPDC1 might interact with KIF20A to promote the occurrence and progression of liposarcoma by activating PI3K/AKT/mTOR signaling pathway.
含DEP结构域蛋白1（DEPDC1）是肿瘤发生和癌症进展的重要促成因素，这一点已广为人知。然而，其在脂肪肉瘤中的潜在致癌机制仍不清楚。
在本研究中，分别利用癌症基因组图谱（TCGA）数据并进行在线Kaplan-Meier分析，评估DEPDC1在肉瘤中的表达及临床相关性。此外，通过实验研究DEPDC1对脂肪肉瘤细胞系细胞功能的影响及其潜在机制。
在此，我们的研究结果显示，与配对的相邻脂肪组织相比，脂肪肉瘤中DEPDC1和KIF20A的表达水平升高，它们的表达与脂肪肉瘤的恶性程度呈正相关。此外，DEPDC1或KIF20A mRNA水平高的患者生存时间较短。实验表明，DEPDC1过表达增强了93T449细胞的增殖、迁移和侵袭能力，而在敲低DEPDC1的SW872细胞中观察到相反的效果。此外，通过STRING预测了DEPDC1的潜在相互作用蛋白，并在脂肪肉瘤细胞中通过免疫共沉淀证实了DEPDC1与KIF20A的相互作用。KIF20A的缺失部分减轻了DEPDC1对脂肪肉瘤细胞恶性表型的促进作用以及PI3K/AKT/mTOR信号通路的激活。
总之，本研究表明DEPDC1可能与KIF20A相互作用，通过激活PI3K/AKT/mTOR信号通路促进脂肪肉瘤的发生和发展。
