GDF11 inhibits the malignant progression of hepatocellular carcinoma via regulation of the mTORC1‑autophagy axis

Wu,Qingyi; Fan,Chan; Liu,Kebo; Tang,Jiefu

doi:10.3892/etm.2024.12540

GDF11 inhibits the malignant progression of hepatocellular carcinoma via regulation of the mTORC1‑autophagy axis

Authors:
- Qingyi Wu
- Chan Fan
- Kebo Liu
- Jiefu Tang
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Affiliations: School of Public Health and Laboratory Medicine, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China, Department of Neurosurgery, Hunan University of Medicine General Hospital, Huaihua, Hunan 418000, P.R. China, Spine and Spinal Cord Center, The First Affiliated Hospital of Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China
Published online on: April 15, 2024 https://doi.org/10.3892/etm.2024.12540
Article Number: 252
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is a common malignant tumor, which is associated with a poor prognosis and high mortality rate. It is well known that growth differentiation factor 11 (GDF11) acts as a tumor suppressor in various types of cancer, including HCC. The present study aimed to determine the tumor‑suppressive properties of GDF11 in HCC and to assess the intrinsic mechanisms. In the present study, the human hepatoma cell line Huh‑7 was transfected with the GDF11 overexpression plasmid (Oe‑GDF11) for gain‑of‑function experiments to investigate the effects of GDF11 on the biological behaviors of HCC cells, including proliferation, colony formation, apoptosis, cell cycle arrest, migration, invasion, epithelial‑mesenchymal transition (EMT) and angiogenesis. The proliferation, colony formation, apoptosis, cell cycle, migration, invasion and angiogenesis of HCC cells were assessed by CCK‑8, EdU staining, colony formation, flow cytometry, wound healing, Transwell and tube formation assays, respectively. Apoptosis‑, cell cycle‑, EMT‑related key factors were also determined by western blot assay. Furthermore, Oe‑GDF11‑transfected Huh‑7 cells were treated with the mammalian target of rapamycin (mTOR) activator MHY1485 for rescue experiments to explore whether GDF11 could exert antitumor effects against HCC via mediating the mTOR complex 1 (mTORC1)‑autophagy axis. In the present study, GDF11 was verified to be lowly expressed in HCC cells. Overexpression of GDF11 inhibited the proliferation, colony formation, migration, invasion, EMT and angiogenesis of HCC cells, and facilitated the apoptosis and cell cycle arrest of HCC cells. Additionally, it was verified that overexpression of GDF11 inactivated the mTORC1 signaling pathway to enhance autophagy in HCC cells. Treatment with the mTOR activator MHY1485 partially reversed the tumor‑suppressive effects of GDF11 overexpression on HCC. In conclusion, GDF11 may exert tumor‑suppressive properties in HCC cells through inactivating the mTORC1 signaling pathway to strengthen autophagy.

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