LncRNA GAS5-hnRNPK axis inhibited ovarian cancer progression via inhibition of AKT signaling in ovarian cancer cells

LncRNA GAS5-hnRNPK 轴通过抑制卵巢癌细胞中的 AKT 信号传导来抑制卵巢癌进展

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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

Background

The incidence of ovarian cancer ranks third among gynecologic malignancies, but the mortality rate ranks first.

Conclusions

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.

Methods

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.

Results

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. Conclusions: 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.

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