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

Hormones and Cancer - Tập 14 - Trang 1-13 - 2023
Te Zhang1,2, Yahui Leng1, Mengjing Duan1,3, Zihang Li1, Yongqing Ma1, Chengyang Huang1, Qin Shi1, Yi Wang1, Chengcheng Wang1, Dandan Liu1, Xuan Zhao4, Shuang Cheng1, Ao Liu1, Yang Zhou1, Jiaqi Liu1, Zhongqiu Pan1, Huimei Zhang1, Li Shen1,5, Hongyan Zhao1,6
1Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China
2Biomedical Research Institute, Hubei University of Medicine, Shiyan, China
3Hengdian Central Health Center, Wuhan, China
4The Second Clinical College, Xi’an Medical University, Xi’an, China
5Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
6Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China

Tóm tắt

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.

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Hormones and Cancer

Tập 14

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