Identification of Mini-chromosome Maintenance 8 As a Potential Prognostic Marker and Its Effects on Proliferation and Apoptosis in Gastric Cancer

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2020 Nov 6

PMID 33155430

Citations 12

Authors

Bin Huang

Minghe Lin

Lisha Lu

Wujin Chen

Jingzhuang Tan

Jinyan Zhao

Zhiyun Cao

Xiaoqin Zhu

Jiumao Lin

Affiliations

Soon will be listed here.

Abstract

Mini-chromosome maintenance (MCM) proteins play important roles in initiating eukaryotic genome replication. The MCM family of proteins includes several members associated with the development and progression of certain cancers. We performed online data mining to assess the expression of MCMs in gastric cancer (GC) and the correlation between their expression and survival in patients with GC. Notably, MCM8 expression was undoubtedly up-regulated in GC, and higher expression correlated with shorter overall survival (OS) and progression-free survival (PFS) in patients with GC. However, the role of MCM8 in GC has not been previously explored. Our in vitro experiments revealed that MCM8 knockdown inhibited cell growth and metastasis. Moreover, MCM8 knockdown induced apoptosis. Mechanistically, the expression levels of Bax and cleaved caspase-3 were increased, whereas Bcl-2 expression decreased. Additionally, we demonstrated that MCM8 knockdown suppressed tumorigenesis in vivo. Overall, these results suggest that MCM8 plays a significant role in GC progression.

Citing Articles

Expression patterns of MCM8 in lung adenocarcinoma and its correlation with key biological processes.

Liu X, Xie J, Wu R, Xiao G, Zhang Y, Pei Z Eur J Med Res. 2025; 30(1):149.

PMID: 40033404 PMC: 11874120. DOI: 10.1186/s40001-025-02407-8.

MCM8 promotes gastric cancer progression through RPS15A and predicts poor prognosis.

Ding L, Sun M, Sun Y, Li J, Zhang Z, Dang S Cancer Med. 2024; 13(13):e7424.

PMID: 38988047 PMC: 11236911. DOI: 10.1002/cam4.7424.

Function and mechanism of MCM8 in the development and progression of colorectal cancer.

Yu S, Dai W, Zhao S, Yang Y, Xu Y, Wang J J Transl Med. 2023; 21(1):623.

PMID: 37710286 PMC: 10503009. DOI: 10.1186/s12967-023-04084-9.

Molecular functions of MCM8 and MCM9 and their associated pathologies.

Helderman N, Terlouw D, Bonjoch L, Golubicki M, Antelo M, Morreau H iScience. 2023; 26(6):106737.

PMID: 37378315 PMC: 10291252. DOI: 10.1016/j.isci.2023.106737.

Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics.

Sun Y, Zhang Y, Shi H, Yang S, Zhao Y, Liu H Hereditas. 2023; 160(1):29.

PMID: 37349788 PMC: 10286446. DOI: 10.1186/s41065-023-00292-x.

References

Peng J, Ding J, Tan C, Baggenstoss B, Zhang Z, Lapolla S . Oligomerization of membrane-bound Bcl-2 is involved in its pore formation induced by tBid. Apoptosis. 2009; 14(10):1145-53. PMC: 2858642. DOI: 10.1007/s10495-009-0389-8. View

Cai L, Zhao K, Yuan X . Expression of minichromosome maintenance 8 in chronic myelogenous leukemia. Int J Clin Exp Pathol. 2016; 8(11):14180-8. PMC: 4713517. View

Nishimura K, Ishiai M, Horikawa K, Fukagawa T, Takata M, Takisawa H . Mcm8 and Mcm9 form a complex that functions in homologous recombination repair induced by DNA interstrand crosslinks. Mol Cell. 2012; 47(4):511-22. DOI: 10.1016/j.molcel.2012.05.047. View

Park J, Long D, Lee K, Abbas T, Shibata E, Negishi M . The MCM8-MCM9 complex promotes RAD51 recruitment at DNA damage sites to facilitate homologous recombination. Mol Cell Biol. 2013; 33(8):1632-44. PMC: 3624244. DOI: 10.1128/MCB.01503-12. View

Labib K, Tercero J, Diffley J . Uninterrupted MCM2-7 function required for DNA replication fork progression. Science. 2000; 288(5471):1643-7. DOI: 10.1126/science.288.5471.1643. View

Tye B . MCM proteins in DNA replication. Annu Rev Biochem. 2000; 68:649-86. DOI: 10.1146/annurev.biochem.68.1.649. View

Lee Y, Miller L, Chan X, Black M, Pang B, Ong C . JMJD6 is a driver of cellular proliferation and motility and a marker of poor prognosis in breast cancer. Breast Cancer Res. 2012; 14(3):R85. PMC: 3446348. DOI: 10.1186/bcr3200. View

Forsburg S . Eukaryotic MCM proteins: beyond replication initiation. Microbiol Mol Biol Rev. 2004; 68(1):109-31. PMC: 362110. DOI: 10.1128/MMBR.68.1.109-131.2004. View

Quan Y, Xia Y, Liu L, Cui J, Li Z, Cao Q . Cell-Cycle-Regulated Interaction between Mcm10 and Double Hexameric Mcm2-7 Is Required for Helicase Splitting and Activation during S Phase. Cell Rep. 2015; 13(11):2576-2586. PMC: 5536962. DOI: 10.1016/j.celrep.2015.11.018. View

10.

Giaginis C, Giagini A, Tsourouflis G, Gatzidou E, Agapitos E, Kouraklis G . MCM-2 and MCM-5 expression in gastric adenocarcinoma: clinical significance and comparison with Ki-67 proliferative marker. Dig Dis Sci. 2010; 56(3):777-85. DOI: 10.1007/s10620-010-1348-5. View

11.

Maiorano D, Cuvier O, Danis E, Mechali M . MCM8 is an MCM2-7-related protein that functions as a DNA helicase during replication elongation and not initiation. Cell. 2005; 120(3):315-28. DOI: 10.1016/j.cell.2004.12.010. View

12.

Hua C, Zhao G, Li Y, Bie L . Minichromosome Maintenance (MCM) Family as potential diagnostic and prognostic tumor markers for human gliomas. BMC Cancer. 2014; 14:526. PMC: 4223428. DOI: 10.1186/1471-2407-14-526. View

13.

Jin B, Robertson K . DNA methyltransferases, DNA damage repair, and cancer. Adv Exp Med Biol. 2012; 754:3-29. PMC: 3707278. DOI: 10.1007/978-1-4419-9967-2_1. View

14.

Vigouroux C, Casse J, Battaglia-Hsu S, Brochin L, Luc A, Paris C . Methyl(R217)HuR and MCM6 are inversely correlated and are prognostic markers in non small cell lung carcinoma. Lung Cancer. 2015; 89(2):189-96. DOI: 10.1016/j.lungcan.2015.05.008. View

15.

Lee K, Im J, Shibata E, Park J, Handa N, Kowalczykowski S . MCM8-9 complex promotes resection of double-strand break ends by MRE11-RAD50-NBS1 complex. Nat Commun. 2015; 6:7744. PMC: 4525285. DOI: 10.1038/ncomms8744. View

16.

Johnson E, Kinoshita Y, Daniel D . A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13. Nucleic Acids Res. 2003; 31(11):2915-25. PMC: 156728. DOI: 10.1093/nar/gkg395. View

17.

Kwok H, Zhang S, McCrudden C, Yuen H, Ting K, Wen Q . Prognostic significance of minichromosome maintenance proteins in breast cancer. Am J Cancer Res. 2015; 5(1):52-71. PMC: 4300722. View

18.

Siddiqui W, Ahad A, Ahsan H . The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Arch Toxicol. 2015; 89(3):289-317. DOI: 10.1007/s00204-014-1448-7. View

19.

Gozuacik D, Chami M, Lagorce D, Faivre J, Murakami Y, Poch O . Identification and functional characterization of a new member of the human Mcm protein family: hMcm8. Nucleic Acids Res. 2003; 31(2):570-9. PMC: 140502. DOI: 10.1093/nar/gkg136. View

20.

Lutzmann M, Grey C, Traver S, Ganier O, Maya-Mendoza A, Ranisavljevic N . MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination. Mol Cell. 2012; 47(4):523-34. DOI: 10.1016/j.molcel.2012.05.048. View