MCMs in Cancer: Prognostic Potential and Mechanisms

Yu, Si; Wang, Guanqun; Shi, Yue; Xu, Haifeng; Zheng, Yongchang; Yang, Chen

doi:10.1155/2020/3750294

Cited by 60 publications

(59 citation statements)

References 95 publications

(136 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that these targeted drugs are non-specific, they affect the entire replication process of normal and tumor cells leading to concomitant death [ 45 ]. Prevailing evidence indicates that MCM family proteins act as helicases in the initial stage of DNA replication, and are key regulators of cell cycle checkpoints [ 46 ]. For instance, MCM2-7 complexes contribute to the initiation of cell cycle, and are therefore potential markers for tumor screening and treatment.…”

Section: Discussionmentioning

confidence: 99%

Elevated expression of minichromosome maintenance 3 indicates poor outcomes and promotes G1/S cell cycle progression, proliferation, migration and invasion in colorectal cancer

et al. 2020

View full text Add to dashboard Cite

Abstract Background: The minichromosome maintenance (MCM) family, a core component of DNA replication, is involved in cell cycle process. Abnormal proliferation has been identified as a crucial process in the evolution of colorectal cancer (CRC). However, the roles of the MCM family in CRC remain largely unknown. Methods: Here, the expression, prognostic significance and functions of the MCM family in CRC were systematically analyzed through a series of online databases including CCLE, Oncomine, HPA, cBioPortal and cancerSEA. Results: We found all MCM family members were highly expressed in CRC, but only elevation of MCM3 expression was associated with poor prognosis of patients with CRC. Further in vitro and in vivo experiments were performed to examine the role of MCM3 in CRC. Analysis of CCLE database and qRT-PCR assay confirmed that MCM3 was overexpressed in CRC cell lines. Moreover, knockdown of MCM3 significantly suppressed transition of G1 to S phase in CRC cells. Furthermore, down-regulation of MCM3 inhibited CRC cell proliferation, migration, invasion and promoted apoptosis. Conclusion: These findings reveal that MCM3 may function as an oncogene and a potential prognosis biomarker. Thus, the association between abnormal expression of MCM3 and the initiation of CRC deserves further exploration.

show abstract

Section: Discussionmentioning

confidence: 99%

Elevated expression of minichromosome maintenance 3 indicates poor outcomes and promotes G1/S cell cycle progression, proliferation, migration and invasion in colorectal cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In cancer cells, the aberrant expression of MCM family members has been reported in a wide range of cancers, and cancer cell malignant phenotypes can be suppressed by knockdown of these genes [ 31 , 32 , 33 , 34 ]. Our recent study showed that siRNA-mediated knockdown of MCM4 attenuated the aggressiveness of lung adenocarcinoma cells [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The MCM Complex as Therapeutic Target

Misono

Mizuno

Shioiri

et al. 2021

Cancers

View full text Add to dashboard Cite

Small cell lung cancer (SCLC) is a highly aggressive cancer, and patients who become refractory to first-line treatment have a poor prognosis. The development of effective treatment regimens is urgently needed. In this study, we identified a gene expression signature of SCLC after treatment failure using SCLC clinical specimens (GEO accession number: GSE162102). A total of 1,136 genes were significantly upregulated in SCLC tissues. These upregulated genes were subjected to KEGG pathway analysis, and “cell cycle”, “Fanconi anemia”, “alcoholism”, “systemic lupus erythematosus”, “oocyte meiosis”, “homologous recombination”, “DNA replication”, and “p53 signaling” were identified as the enriched pathways among the genes. We focused on the cell cycle pathway and investigated the clinical significance of four genes associated with this pathway: minichromosome maintenance (MCM) 2, MCM4, MCM6, and MCM7. The overexpression of these MCM genes was confirmed in SCLC clinical specimens. Knockdown assays using siRNAs targeting each of these four MCM genes showed significant attenuation of cancer cell proliferation. Moreover, siRNA-mediated knockdown of each MCM gene enhanced the cisplatin sensitivity of SCLC cells. Our SCLC molecular signature based on SCLC clinical specimens after treatment failure will provide useful information to identify novel molecular targets for this disease.

show abstract

“… 22 Recent studies have suggested that dysregulated MCMs lead to tumor initiation, progression, and chemoresistance via modulating cell cycle and DNA replication stress. 23 , 24 Overexpressed MCMs are detected in various cancer tissues and are potential biomarkers for the diagnosis and prognosis of many kinds of cancers. Wu et al 25 found that high levels of MCM2 were observed in LUSC and associated with adverse tumor features.…”

Section: Discussionmentioning

confidence: 99%

Silencing HIPPI Suppresses Tumor Progression in Non-Small-Cell Lung Cancer by Inhibiting DNA Replication

Xie¹,

Li²,

Jiang³

et al. 2021

OTT

View full text Add to dashboard Cite

Introduction Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 80%–85% of all cases of lung cancer. Huntingtin interacting protein-1 interacting protein (HIPPI) is a transcription regulator and plays an important role in apoptotic cell death. However, the role of HIPPI in NSCLC remains unclear. Methods Immunohistochemistry (IHC) and qRT-PCR were performed for expression analysis. The roles of HIPPI were studied using cell counting kit-8 (CCK-8), colony formation, flow cytometry, wound healing, Transwell invasion assays and mouse xenograft model. Gene microarray analysis and bioinformatics analysis were used to identify differentially expressed genes after HIPPI silencing. Results HIPPI is highly expressed in NSCLC tissues relative to adjacent normal tissues. Targeting HIPPI by RNA interference inhibits NSCLC cell proliferation in vitro and tumor growth in vivo. HIPPI silencing also attenuates cell migration and invasion and enhances cisplatin sensitivity in NSCLC cells. Mechanistic investigation suggests that HIPPI can positively regulate the expression of MCM2, MCM6 and MCM8, which are key regulators of DNA replication. Furthermore, consistent with HIPPI, MCM2, MCM6 and MCM8 are also upregulated in NSCLC tissues. Conclusion Our study highlights the importance of HIPPI for tumor biology in NSCLC and suggests that HIPPI may be a potential therapeutic target for NSCLC treatment.

show abstract

MCMs in Cancer: Prognostic Potential and Mechanisms

Cited by 60 publications

References 95 publications

Elevated expression of minichromosome maintenance 3 indicates poor outcomes and promotes G1/S cell cycle progression, proliferation, migration and invasion in colorectal cancer

Elevated expression of minichromosome maintenance 3 indicates poor outcomes and promotes G1/S cell cycle progression, proliferation, migration and invasion in colorectal cancer

Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The MCM Complex as Therapeutic Target

Silencing HIPPI Suppresses Tumor Progression in Non-Small-Cell Lung Cancer by Inhibiting DNA Replication

Contact Info

Product

Resources

About