MCM7 amplification and overexpression promote cell proliferation, colony formation and migration in esophageal squamous cell carcinoma by activating the AKT1/mTOR signaling pathway

Qiu, Yuntan; Wang, Wenjun; Zhang, Bing; Mei, Li-Li; Shi, Zhi‐Zhou

doi:10.3892/or.2017.5614

Cited by 37 publications

(37 citation statements)

References 34 publications

(34 reference statements)

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“…Knockdown of MCM6 was related to a delay in S/G2-phase progression with downregulation of CDK2, CDK4, CyclinA, CyclinB1, CyclinD1, and CyclinE in HCC [86]. Silencing of MCM7 reduced cyclinD1, cyclinE2, and CDK2 [58], which triggered events in the G1 or G1/S phase. Another experiment indicated that MCM8 bound to cyclin D1 to active Rb protein phosphorylation by Cdk4, and the binding allowed the entry into the S phase [51].…”

Section: Effects Of Mcms In Cellular Signalingmentioning

confidence: 97%

“…AKT is a serine/threonine kinase involved in the regulation of cell metabolism, proliferation, and survival. Silencing of MCM7 inhibited the phosphorylation of AKT1 and mTOR in both esophageal cancer cell lines, suggesting that MCM7 might promote cancer development and poor survival outcomes via activating the AKT1/mTOR signaling pathway [58]. Implicated genes and pathways in lymphoblastic lymphoma of MCM2-deficient mice include Pten, Tcfe2a, Mbd3, Setd1b, and Notch signaling pathway [36].…”

Section: Effects Of Mcms In Cellular Signalingmentioning

confidence: 99%

“…Moreover, MCMs may mediate DNA damage repair. Knockdown of MCM genes was reported to significantly inhibit cell proliferation [50,57,58]. Based on the biological and functional significance of MCMs, many MCM-targeted drugs have been developed.…”

Section: Mcms As Diagnostic Markers and Therapeutic Targetsmentioning

confidence: 99%

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MCMs in Cancer: Prognostic Potential and Mechanisms

Wang

Shi

et al. 2020

Analytical Cellular Pathology

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Enabling replicative immortality and uncontrolled cell cycle are hallmarks of cancer cells. Minichromosome maintenance proteins (MCMs) exhibit helicase activity in replication initiation and play vital roles in controlling replication times within a cell cycle. Overexpressed MCMs are detected in various cancerous tissues and cancer cell lines. Previous studies have proposed MCMs as promising proliferation markers in cancers, while the prognostic values remain controversial and the underlying mechanisms remain unascertained. This review provides an overview of the significant findings regarding the cellular and tumorigenic functions of the MCM family. Besides, current evidence of the prognostic roles of MCMs is retrospectively reviewed. This work also offers insight into the mechanisms of MCMs prompting carcinogenesis and adverse prognosis, providing information for future research. Finally, MCMs in liver cancer are specifically discussed, and future perspectives are provided.

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Section: Effects Of Mcms In Cellular Signalingmentioning

confidence: 97%

Section: Effects Of Mcms In Cellular Signalingmentioning

confidence: 99%

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MCMs in Cancer: Prognostic Potential and Mechanisms

Wang

Shi

et al. 2020

Analytical Cellular Pathology

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“…Currently, there is still lack of previous studies on the relationship between MCM7 and CRC. Though, many studies have shown that MCM7 proteins are involved in tumorigenesis [10]. MCM7 regulated the proliferation and migration of esophageal squamous cell carcinoma cells by activating the AKT1/mTOR pathway [11].…”

Section: Discussionmentioning

confidence: 99%

“…The minichromosome maintenance (MCM) complex is composed of six highly conservative MCM proteins, named MCM2-7(small body maintenance complex component 2-7), which is necessary to initiate DNA replication. MCM is a marker associated with proliferation of several types of cancer [6,10]. MCM2-7 forms the pre-replication complex (pre-RC), and then recognizes the origin recognition complex (ORC) before DNA replication [11].…”

Section: Introductionmentioning

confidence: 99%

Up-Regulated Expression of MCM7 is a Poor Prognostic Factor in Colorectal Cancer

Dong¹,

Wang²,

Xu³

et al. 2019

CSROA

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Objective: Colorectal cancer (CRC) is one of the most common malignancies worldwide. MCM7 is one of the important components of DNA replication complex involved in cancer progression. At present, the significance of MCM7 and its mechanisms in CRC development are still unclear. Materials and Methods:Gene expression data of CRC was downloaded from Gene Expression Omnibus (GEO) and TCGA databases. Bioinformatics method was applied to screen CRC differentially expressed genes (DEGs). MCODE and degree value analysis were used to select core genes. The datasets were explored to verify the mRNA expression level of MCM7, and the protein expression level of MCM7 was further verified by Western Blotting and immunohistochemical analysis. Moreover, we also analyzed the correlation between MCM7 and clinical characteristics. The prognostic value of MCM7 in CRC was explored through Kaplan-Meier analysis, univariate and multivariate Cox regression analysis. Results:We confirmed that MCM7 was up-regulated in CRC tissues compared with adjacent non-tumor tissues. MCM7 overexpression was positively associated with lymph node metastasis and TNM stage in CRC. Higher expression of MCM7 showed shorter overall survival rate. Furthermore, MCM7 level could be an independent prognostic factor for CRC. Conclusion:Our study suggested that MCM7 may be a new prognostic factor or molecular target in CRC.The R package 'edgeR' and'limma' were applied to identify the DEGs between CRC tissues and normal tissues. The inclusion standard of DEGs from TCGA was adjusted P <0.01 and log2 Fold Change (FC)>2. DEGs from GEO datasets were selected with the criterion of combined adjusted p< 0.01 and log2FC >1 or log2FC>0.58. Protein-protein interaction (PPI) network construction and module analysisSTRING (https://string-db.org) was applied to construct PPI network for DEGs with confidence score>0.4 and p<0.01. Cytoscape software was used to visualize network. Another, the Molecular Complex Detection (MCODE) app was used to screen modules of PPI network in Cytoscape under degree cutoff =2, node score cutoff=0.2, k-core=2, and max.depth=100. Moreover, the nodes were calculated the degree value.

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MCM7 silencing promotes cutaneous melanoma cell autophagy and apoptosis by inactivating the AKT1/mTOR signaling pathway

Yang

et al. 2019

J of Cellular Biochemistry

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Cutaneous melanoma (CM) has become a major public health concern. Studies illustrate that minichromosome maintenance protein 7 (MCM7) participate in various diseases including skin disease. Our study aimed to study the effects of MCM7 silencing on CM cell autophagy and apoptosis by modulating the AKT threonine kinase 1 (AKT1)/mechanistic target of rapamycin kinase (mTOR) signaling pathway. Initially, microarray analysis was used to screen the CM‐related gene expression data as well as differentially expressed genes. Subsequently, MCM7 expression vector and lentivirus RNA used for MCM7 silencing (LV‐shRNA‐MCM7) were constructed, and these vectors, dimethyl sulfoxide (DMSO) and AKT activator SC79 were then introduced into CM cell line SK‐MEL‐2 to validate the role of MCM7 in cell autophagy, viability, apoptosis, cell cycle, migration, and invasion. To further investigate the regulatory mechanisms of MCM7 in CM progress, the expression of MCM7, AKT1, mTOR, cyclin D1, as well as autophagy and apoptosis relative factors, such as LC3B, SOD2, DJ‐1, p62, Bcl‐2, Bax, and caspase‐3 in melanoma cells was determined. MCM7 might mediate the AKT1/mTOR signaling pathway to influence the progress of melanoma. MCM7 silencing contributed to the increased expression of Bax, capase‐3, and autophagy‐related genes (LC3B, SOD2, and DJ‐1), but decreased the expression of Bcl‐2, which suggested that MCM7 silencing promoted autophagy and cell apoptosis. At the same time, MCM7 silencing also attenuated cell viability, invasion, and migration, and reduced the cyclin D1 expression and protein levels of p‐AKT1 and p‐mTOR. Taken together, MCM7 silencing inhibited CM via inactivation of the AKT1/mTOR signaling pathway.

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MCM7 amplification and overexpression promote cell proliferation, colony formation and migration in esophageal squamous cell carcinoma by activating the AKT1/mTOR signaling pathway

Cited by 37 publications

References 34 publications

MCMs in Cancer: Prognostic Potential and Mechanisms

MCMs in Cancer: Prognostic Potential and Mechanisms

Up-Regulated Expression of MCM7 is a Poor Prognostic Factor in Colorectal Cancer

MCM7 silencing promotes cutaneous melanoma cell autophagy and apoptosis by inactivating the AKT1/mTOR signaling pathway

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