Silencing of keratin 15 impairs viability and mobility while facilitating the doxorubicin chemosensitivity by inactivating the β‑catenin pathway in liver cancer

Wang,Junying; Zhu,Guangyu

doi:10.3892/ol.2023.14034

Silencing of keratin 15 impairs viability and mobility while facilitating the doxorubicin chemosensitivity by inactivating the β‑catenin pathway in liver cancer

Authors:
- Junying Wang
- Guangyu Zhu
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Affiliations: Department of Interventional Radiology and Vascular Surgery, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
Published online on: August 30, 2023 https://doi.org/10.3892/ol.2023.14034
Article Number: 447
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Keratin 15 (KRT15) regulates the invasion as well as the stemness and is associated with tumor size and metastasis of several gastrointestinal cancers apart from liver cancer. The present study aimed to explore the effect of KRT15 knockdown on liver cancer malignant behaviors and its interaction with the β‑catenin pathway. Small interfering (si)‑KRT15 and si‑negative control (NC) were transfected into liver cancer cell lines, followed by the addition or not of CHIR‑99021 (a β‑catenin agonist). Cell viability, invasion, apoptosis, and the half maximal inhibitory concentration (IC50) value of doxorubicin (Dox) were then assessed. The present study illustrated that KRT15 gene and protein expression levels were upregulated in most liver cancer cell lines (Huh7, PLC, Hep3B and HepG2) compared to the normal liver cell line THLE‑2. si‑KRT15 reduced cell viability and invasive cell count while promoting the apoptosis rate in Huh7 and HepG2 cells. In addition, si‑KRT15 also reduced the IC₅₀ value of Dox. Furthermore, si‑KRT15 inactivated the β‑catenin pathway as reflected by β‑catenin, cyclin D1 and c‑Myc expression levels in Huh7 and HepG2 cells. Subsequently, CHIR‑99021 treatment increased the cell viability and invasive cell count while reducing the apoptosis rate in Huh7 and HepG2 cells. Concurrently, the IC₅₀ value of Dox was also increased. Notably, CHIR‑99021 treatment attenuated the effect of si‑KRT15 on mediating the aforementioned Huh7 and HepG2 cell malignant behaviors and Dox chemosensitivity. In conclusion, KRT15 knockdown suppressed viability and mobility but facilitated Dox chemosensitivity via inactivating the β‑catenin pathway in liver cancer, suggesting its potential as a target for liver cancer treatment.

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