Downregulation of MCM8 expression restrains the malignant progression of cholangiocarcinoma

Hao,Jingcheng; Deng,Haimin; Yang,Yuan; Chen,Lidan; Wu,Qiang; Yao,Pei; Li,Junen; Li,Bowen; Jin,Xueli; Wang,Haiqing; Duan,Huaxin

doi:10.3892/or.2021.8186

Downregulation of MCM8 expression restrains the malignant progression of cholangiocarcinoma

Authors:
- Jingcheng Hao
- Haimin Deng
- Yuan Yang
- Lidan Chen
- Qiang Wu
- Pei Yao
- Junen Li
- Bowen Li
- Xueli Jin
- Haiqing Wang
- Huaxin Duan
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Affiliations: Department of Hepatobiliary and Vascular Surgery, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, Department of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China, Department of Rheumatology and Immunology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, Department of Hepatopancreatobiliary Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610041, P.R. China
Published online on: September 15, 2021 https://doi.org/10.3892/or.2021.8186
Article Number: 235
Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor with an extremely poor prognosis. Minichromosome maintenance 8 homologous recombination repair factor (MCM8) is a helicase involved in the elongation step of DNA replication and tumorigenesis. In the present study, the clinical significance and biological function of MCM8 in CCA were investigated. The expression levels of MCM8 in CCA and paracancerous tissues were analyzed using immunohistochemical staining. The potential mechanisms underlying MCM8 and the biological effects of MCM8 in CCA cells were explored using in vitro assays and in vivo mouse xenograft models. The high expression levels of MCM8 in CCA has important clinical significance in predicting disease progression. Knockdown of MCM8 decreased proliferation, promoted apoptosis and suppressed migration of CCA cells. MCM8 knockdown also suppressed tumor growth in vivo. Mechanistically, MCM8 knockdown led to the abnormal downregulation of survivin, XIAP, HSP27, IGF‑1sR, sTNF‑R1, sTNF‑R2, TNF‑α and TNF‑β. Furthermore, downregulation of MCM8 expression inhibited the PI3K/Akt signaling pathway and induced the MAPK9 signaling pathway. MCM8 promoted the malignant progression of CCA, indicating that inhibition of MCM8 may have the potential to serve as a novel molecular targeted therapy.

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