RNF125‑mediated ubiquitination of MCM6 regulates the proliferation of human liver hepatocellular carcinoma cells

Feng,Xueyi; Song,Dongqiang; Liu,Xiaolan; Liang,Yongkang; Jiang,Pin; Wu,Shenwei; Liu,Fubao

doi:10.3892/ol.2024.14238

RNF125‑mediated ubiquitination of MCM6 regulates the proliferation of human liver hepatocellular carcinoma cells

Authors:
- Xueyi Feng
- Dongqiang Song
- Xiaolan Liu
- Yongkang Liang
- Pin Jiang
- Shenwei Wu
- Fubao Liu
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Liver Cancer Institute, Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China, Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of General Surgery, Lu'an Affiliated Hospital of Anhui Medical University, Lu'an, Anhui 237005, P.R. China
Published online on: January 17, 2024 https://doi.org/10.3892/ol.2024.14238
Article Number: 105
Copyright: © Feng 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 the third leading cause of cancer‑associated mortality worldwide. Minichromosome maintenance proteins (MCMs), particularly MCM2‑7, are upregulated in various cancers, including HCC. The aim of the present study was to investigate the role of MCM2‑7 in human liver HCC (LIHC) and the regulation of the protein homeostasis of MCM6 by a specific E3 ligase. Bioinformatics analyses demonstrated that MCM2‑7 were highly expressed in LIHC compared with corresponding normal tissues at the mRNA and protein levels, and patients with LIHC and high mRNA expression levels of MCM2, MCM3, MCM6 and MCM7 had poor overall survival rates. Cell Counting Kit‑8 and colony formation assays revealed that the knockdown of MCM2, MCM3, MCM6 or MCM7 in Huh7 and Hep3B HCC cells inhibited cell proliferation and colony formation. In addition, pull‑down, co‑immunoprecipitation and ubiquitination assays demonstrated that RNF125 interacts with MCM6 and mediates its ubiquitination. Furthermore, co‑transfection experiments indicated that RNF125 promoted the proliferation of HCC cells mainly through MCM6. In summary, the present study suggests that the RNF125‑MCM6 axis plays an important role in the regulation of HCC cell proliferation and is a promising therapeutic target for the treatment of LIHC.

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