LncRNA GAS5-hnRNPK轴通过抑制卵巢癌细胞中的AKT信号传导抑制了卵巢癌的进展。
LncRNA GAS5-hnRNPK axis inhibited ovarian cancer progression via inhibition of AKT signaling in ovarian cancer cells.
发表日期：2023 Aug 28
作者：
Te Zhang, Yahui Leng, Mengjing Duan, Zihang Li, Yongqing Ma, Chengyang Huang, Qin Shi, Yi Wang, Chengcheng Wang, Dandan Liu, Xuan Zhao, Shuang Cheng, Ao Liu, Yang Zhou, Jiaqi Liu, Zhongqiu Pan, Huimei Zhang, Li Shen, Hongyan Zhao
来源：
Cellular & Molecular Immunology
摘要：
卵巢癌的发病率在妇科恶性肿瘤中排名第三，但死亡率排名第一。根据公共卵巢癌数据库，GAS5在卵巢癌中表达水平低，与卵巢癌患者的低生存率相关。在OVCAR3和A2780细胞中，GAS5过表达通过影响增殖和迁移能力抑制卵巢恶性肿瘤。GAS5过表达增加了细胞凋亡率，并通过流式细胞仪评估细胞在G1期停滞。基于RNA-pulldown和质谱分析，我们发现hnRNPK是一个潜在的靶基因，受GAS5的负调控。机制上，GAS5通过抑制PI3K/AKT/mTOR通路并结合hnRNPK蛋白影响hnRNPK稳定性。此外，救援实验表明hnRNPK在卵巢癌进程中具有显著作用。我们的研究揭示了GAS5通过下调hnRNPK表达来抑制卵巢癌转移的机制，并且GAS5可用于预测卵巢癌患者的预后。
© 2023. Springer Science+Business Media, LLC.
The incidence of ovarian cancer ranks third among gynecologic malignancies, but the mortality rate ranks first.The expression of GAS5 is low in ovarian cancer and is associated with the low survival of ovarian cancer patients according to public ovarian cancer databases. GAS5 overexpression inhibited ovarian malignancy by affecting the proliferation and migratory abilities in OVCAR3 and A2780 cells. GAS5 overexpression increased the rate of cell apoptosis, and the cells were blocked in the G1 phase as assessed by flow cytometry.We found that hnRNPK was a potential target gene, which was regulated negatively by GAS5 based on RNA-pulldown and mass spectrometry analysis. Mechanistically, GAS5 affected the inhibition of the PI3K/AKT/mTOR pathways and bound the protein of hnRNPK, which influenced hnRNPK stability. Furthermore, rescue assays demonstrated hnRNPK was significantly involved in the progression of ovarian cancer.Our study showed one of the mechanisms that GAS5 inhibited ovarian cancer metastasis by down-regulating hnRNPK expression, and GAS5 can be used to predict the prognosis of ovarian cancer patients.© 2023. Springer Science+Business Media, LLC.