PMID- 37185675
OWN - NLM
STAT- MEDLINE
DCOM- 20230626
LR  - 20231124
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 44
IP  - 4
DP  - 2023 Jun 24
TI  - MCM6 promotes intrahepatic cholangiocarcinoma progression by upregulating E2F1 
      and enhancing epithelial-mesenchymal transition.
PG  - 279-290
LID - 10.1093/carcin/bgad023 [doi]
AB  - Minichromosome maintenance complex component 6 (MCM6), a member of the MCM 
      family, plays a pivotal role in DNA replication initiation and genome duplication 
      of proliferating cells. MCM6 is upregulated in multiple malignancies and is 
      considered a novel diagnostic biomarker. However, the functional contributions 
      and prognostic value of MCM6 in intrahepatic cholangiocarcinoma (ICC) remain 
      unexplored. In this study, we investigated the molecular function of MCM6 in ICC. 
      Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO, 
      GSE107943) indicated an upregulation of MCM6 in tumor tissues. 
      Immunohistochemical analysis performed on 115 cases of ICC samples confirmed the 
      upregulation of MCM6 and further suggested that a high level of MCM6 expression 
      predicted shorter overall and disease-free survival in ICC patients. Functional 
      studies suggested that MCM6 knockdown significantly suppressed cell viability, 
      blocked cell cycle progression and inhibited metastasis, while the enhancement of 
      MCM6 expression promoted the proliferation and migration of ICC cells both in 
      vitro and in vivo. Mechanistically, Gene Set Enrichment Analysis (GSEA) suggested 
      that the epithelial-mesenchymal transition (EMT) and E2F1-correlated genes were 
      enriched in ICC tissues with high MCM6 expression. Further verification indicated 
      that MCM6 promoted the EMT of ICC cells via upregulating E2F1. In addition, E2F1 
      knockdown partially blocked the pro-malignant effects of MCM6 overexpression. In 
      summary, MCM6 was found to be a novel prognostic and predictive marker for ICC. 
      MCM6 promoted ICC progression via activation of E2F1-mediated EMT.
CI  - (c) The Author(s) 2023. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Gao, Chongqing
AU  - Gao C
AD  - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 
      Guangdong 510630, China.
FAU - Li, Jing
AU  - Li J
AD  - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 
      Guangdong 510630, China.
FAU - Zeng, Fuling
AU  - Zeng F
AD  - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 
      Guangdong 510630, China.
FAU - Wang, Lijuan
AU  - Wang L
AD  - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 
      Guangdong 510630, China.
FAU - Chen, Kaiyun
AU  - Chen K
AD  - Department of General Surgery, Guangzhou Hospital of Integrated Traditional and 
      West Medicine, Guangzhou, Guangdong 510632, China.
FAU - Chen, Dong
AU  - Chen D
AD  - Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun 
      Yat-sen University, Guangzhou, Guangdong 510632, China.
FAU - Hong, Jian
AU  - Hong J
AD  - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 
      Guangdong 510630, China.
AD  - Department of General Surgery, Guangdong Second Provincial General Hospital, 
      Guangzhou, Guangdong 510317, China.
FAU - Qu, Chen
AU  - Qu C
AUID- ORCID: 0000-0002-6539-3197
AD  - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 
      Guangdong 510630, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - EC 3.6.4.12 (Minichromosome Maintenance Complex Component 6)
RN  - EC 3.6.4.12 (MCM6 protein, human)
RN  - 0 (E2F1 protein, human)
RN  - 0 (E2F1 Transcription Factor)
SB  - IM
MH  - Humans
MH  - Minichromosome Maintenance Complex Component 6/genetics/metabolism
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Prognosis
MH  - *Cholangiocarcinoma/pathology
MH  - *Bile Duct Neoplasms/pathology
MH  - Bile Ducts, Intrahepatic/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - E2F1 Transcription Factor/genetics
EDAT- 2023/05/15 19:12
MHDA- 2023/06/26 06:42
CRDT- 2023/05/15 13:45
PHST- 2022/10/24 00:00 [received]
PHST- 2022/12/22 00:00 [revised]
PHST- 2023/04/21 00:00 [accepted]
PHST- 2023/06/26 06:42 [medline]
PHST- 2023/05/15 19:12 [pubmed]
PHST- 2023/05/15 13:45 [entrez]
AID - 7142844 [pii]
AID - 10.1093/carcin/bgad023 [doi]
PST - ppublish
SO  - Carcinogenesis. 2023 Jun 24;44(4):279-290. doi: 10.1093/carcin/bgad023.