机构：[1]Department of Hepatobiliary and Vascular Surgery, Clinical Medical College and The First Affiliated Hospital ofChengdu Medical College, Chengdu, Sichuan 610500[2]Department of Oncology, Hunan Provincial People's Hospital,The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005[3]Department of Rheumatology andImmunology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College,Chengdu, Sichuan 610500[4]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 610041四川省人民医院四川省肿瘤医院[5]Key laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province,Hunan Normal University, Changsha, Hunan 410013[6]Laboratory of Oncology, Institute of Translational Medicine,Hunan Provincial People's Hospital, Changsha, Hunan 410005, P.R. China
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-alpha and TNF-beta. 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.
基金：
Institutional Research Funding from The First Affiliated Hospital of Chengdu Medical College [CYFY-GQ20]
第一作者机构：[1]Department of Hepatobiliary and Vascular Surgery, Clinical Medical College and The First Affiliated Hospital ofChengdu Medical College, Chengdu, Sichuan 610500
通讯作者：
通讯机构：[2]Department of Oncology, Hunan Provincial People's Hospital,The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005[5]Key laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province,Hunan Normal University, Changsha, Hunan 410013[6]Laboratory of Oncology, Institute of Translational Medicine,Hunan Provincial People's Hospital, Changsha, Hunan 410005, P.R. China[*1]Department of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61 Jiefang West Road, Changsha, Hunan 410005, P.R. China
推荐引用方式(GB/T 7714)：
JINGCHENG HAO,HAIMIN DENG,YUAN YANG,et al.Downregulation of MCM8 expression restrains the malignant progression of cholangiocarcinoma[J].ONCOLOGY REPORTS.2021,46(5):doi:10.3892/or.2021.8186.
APA：
JINGCHENG HAO,HAIMIN DENG,YUAN YANG,LIDAN CHEN,QIANG WU...&HUAXIN DUAN.(2021).Downregulation of MCM8 expression restrains the malignant progression of cholangiocarcinoma.ONCOLOGY REPORTS,46,(5)
MLA：
JINGCHENG HAO,et al."Downregulation of MCM8 expression restrains the malignant progression of cholangiocarcinoma".ONCOLOGY REPORTS 46..5(2021)
