Knockdown of KRT17 decreases osteosarcoma cell proliferation and the Warburg effect via the AKT/mTOR/HIF1α pathway

Yan,Xianke; Yang,Chao; Hu,Wei; Chen,Tao; Wang,Qi; Pan,Feng; Qiu,Bing; Tang,Bensen

doi:10.3892/or.2020.7611

Knockdown of KRT17 decreases osteosarcoma cell proliferation and the Warburg effect via the AKT/mTOR/HIF1α pathway

Authors:
- Xianke Yan
- Chao Yang
- Wei Hu
- Tao Chen
- Qi Wang
- Feng Pan
- Bing Qiu
- Bensen Tang
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Affiliations: Department of Orthopedics, Guizhou Provincial Orthopedics Hospital, Guiyang, Guizhou 550000, P.R. China
Published online on: May 12, 2020 https://doi.org/10.3892/or.2020.7611
Pages: 103-114
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Keratins are fibrous structural proteins that serve essential roles in forming the stratum corneum and protect the cells in this layer of skin from damage. Keratin 17 (KRT17) is a key member of the keratins, and dysregulated expression of KRT17 has been reported in various types of cancer, such as lung and gastric cancer. The present study aimed to identify the role of KRT17 in osteosarcoma and the underlying molecular mechanism. The expression of KRT17 in osteosarcoma tissues and cell lines was detected using reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. The effects of KRT17 on osteosarcoma cell proliferation and the Warburg effect in vitro were detected using CCK‑8 and colony formation assays, cell cycle distribution analysis and metabolic measures. The effects of KRT17 on osteosarcoma cell proliferation in vivo were detected using a subcutaneous tumorigenesis model. The association between KRT17 and the AKT/mTOR/hypoxia‑inducible factor 1α (HIF1α) pathway was detected using RT‑qPCR and western blotting. The results demonstrated that KRT17 was highly expressed in osteosarcoma tissues and cell lines. Knockdown of KRT17 decreased osteosarcoma cell proliferation and colony formation, induced G1 phase arrest and inhibited glycolysis in vitro. Similarly, the suppression of KRT17 decreased osteosarcoma tumor growth in vivo. Knockdown of KRT17 decreased the expression of phosphorylated (p)‑AKT, p‑mTOR, HIF1α and the target gene of HIF1α glucose transporter 1. Restoring the expression of p‑AKT, p‑mTOR or HIF1α reversed the effect of KRT17 inhibition on cell proliferation and glycolysis. These results indicated that knockdown of KRT17 may be an effective method for treating osteosarcoma through inhibiting osteosarcoma cell proliferation and the Warburg effect by suppressing the AKT/mTOR/HIF1α pathway.

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