Knockdown of minichromosome maintenance proteins inhibits foci forming of mediator of DNA-damage checkpoint 1 in response to DNA damage in human esophageal squamous cell carcinoma TE-1 cells

Yu, Jinzhong; Wang, Ruijie; Wu, Jinfeng; Dang, Zhongqin; Zhang, Qinsheng; Li, Bo

doi:10.1134/s0006297916100205

Cited by 6 publications

(2 citation statements)

References 29 publications

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“…The research found MCM6 was an oncogene and could promote esophageal cancer cells proliferation 33 . Knockdown of MCM6 could significantly inhibit the forming of mediator of DNA-damage checkpoint 1, causing the DNA repair defects and decreased proliferation in esophageal cancer cells 33 , 34 . Our results were similar to their findings, unraveling the MCM6 was upregulated in EAC tissues and played an oncogenic role.…”

Section: Discussionmentioning

confidence: 99%

Novel evidence of obesity paradox in esophageal adenocarcinoma: perspective on genes that uncouple adiposity from dismal outcomes

Zhu¹,

Yang²,

Dong³

et al. 2022

J. Cancer

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Background: Obesity is a strong risk factor for esophageal adenocarcinoma (EAC). Nevertheless, not all the patients with EAC are obesity, and a substantial proportion of obesity patients don't suffer from poor prognoses. The mechanisms behind the "obesity paradox" that uncouple obesity from dismal outcomes in EAC are unclear. This study aimed to explore the "obesity-guarding" genes (OGG) profiles and their prognostic values in patients with EAC. Methods: Gene expression data and clinical information of patients with EAC were downloaded from The Cancer Genome Atlas (TCGA) database. Enrichment analysis was used to explore the OGG functions and pathways. Cox regression analysis and nomogram model were performed to investigate the OGG prognostic values for overall survival (OS). In addition, relations between OGG and immune cells were assessed by the "CIBERSORT" algorithm and the Tumor IMmune Estimation Resource (TIMER) tool. Finally, the results were experimentally validated in real-world study. Results: A total of 69 OGG were retrieved, and 17 significantly differentially expressed genes (SDEG) were identified between normal and EAC tissues. Enrichment analysis showed the OGG were enriched in the mitochondrion-related and various receptor pathways. Univariate Cox regression results showed that the MCM6, ATXN2 and CSK were significantly associated with OS (P=0.036, 0.039, 0.046, respectively). Multivariate Cox regression analysis showed MCM6 and CSK were independent prognostic genes for OS (P=0.025, 0.041, respectively). Nomogram demonstrated that the OGG had good predictive abilities for the 1-, 2-, and 3-year OS. Immunity analysis demonstrated that OGG were significantly associated with immune cells (P <0.05). In addition, clinical correlation analysis revealed that the OGG had significant relations with clinical parameters (P <0.05). The experiment results confirmed that the SDEG were significantly different between normal and EAC tissues (P <0.05). Conclusions: We identified the OGG expression profiles that may uncouple obesity from poor survival in patients with EAC. They have prognostic values in predicting patients' OS, and may be exploited for prognostic biomarkers.

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Section: Discussionmentioning

confidence: 99%

Novel evidence of obesity paradox in esophageal adenocarcinoma: perspective on genes that uncouple adiposity from dismal outcomes

Zhu¹,

Yang²,

Dong³

et al. 2022

J. Cancer

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“…In addition, the MCM6 gene is involved in tumor pathogenesis 16 and promotes the progression of hepatocellular carcinoma (HCC) 14 . It also plays a vital role in cell proliferation, migration, invasion and the immune response in many cancer types, such as breast cancer 17 , 18 , HCC 16 , glioma 19 , esophageal squamous cell carcinoma (ESCC) 20 and endometrioid endometrial adenocarcinoma 21 . The MCM7 gene plays a significant role in eukaryotic DNA replication, and its overexpression is related to cellular proliferation and responsible for various cancers 22 .…”

Section: Introductionmentioning

confidence: 99%

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

Kamal,

Mia,

Faruque

et al. 2024

Sci Rep

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Single nucleotide polymorphisms (SNPs) are one of the most common determinants and potential biomarkers of human disease pathogenesis. SNPs could alter amino acid residues, leading to the loss of structural and functional integrity of the encoded protein. In humans, members of the minichromosome maintenance (MCM) family play a vital role in cell proliferation and have a significant impact on tumorigenesis. Among the MCM members, the molecular mechanism of how missense SNPs of minichromosome maintenance complex component 6 (MCM6) contribute to DNA replication and tumor pathogenesis is underexplored and needs to be elucidated. Hence, a series of sequence and structure-based computational tools were utilized to determine how mutations affect the corresponding MCM6 protein. From the dbSNP database, among 15,009 SNPs in the MCM6 gene, 642 missense SNPs (4.28%), 291 synonymous SNPs (1.94%), and 12,500 intron SNPs (83.28%) were observed. Out of the 642 missense SNPs, 33 were found to be deleterious during the SIFT analysis. Among these, 11 missense SNPs (I123S, R207C, R222C, L449F, V456M, D463G, H556Y, R602H, R633W, R658C, and P815T) were found as deleterious, probably damaging, affective and disease-associated. Then, I123S, R207C, R222C, V456M, D463G, R602H, R633W, and R658C missense SNPs were found to be highly harmful. Six missense SNPs (I123S, R207C, V456M, D463G, R602H, and R633W) had the potential to destabilize the corresponding protein as predicted by DynaMut2. Interestingly, five high-risk mutations (I123S, V456M, D463G, R602H, and R633W) were distributed in two domains (PF00493 and PF14551). During molecular dynamics simulations analysis, consistent fluctuation in RMSD and RMSF values, high Rg and hydrogen bonds in mutant proteins compared to wild-type revealed that these mutations might alter the protein structure and stability of the corresponding protein. Hence, the results from the analyses guide the exploration of the mechanism by which these missense SNPs of the MCM6 gene alter the structural integrity and functional properties of the protein, which could guide the identification of ways to minimize the harmful effects of these mutations in humans.

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MCM family in gastrointestinal cancer and other malignancies: From functional characterization to clinical implication

Wang

Chen

Zhang

et al. 2020

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Knockdown of minichromosome maintenance proteins inhibits foci forming of mediator of DNA-damage checkpoint 1 in response to DNA damage in human esophageal squamous cell carcinoma TE-1 cells

Cited by 6 publications

References 29 publications

Novel evidence of obesity paradox in esophageal adenocarcinoma: perspective on genes that uncouple adiposity from dismal outcomes

Novel evidence of obesity paradox in esophageal adenocarcinoma: perspective on genes that uncouple adiposity from dismal outcomes

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

MCM family in gastrointestinal cancer and other malignancies: From functional characterization to clinical implication

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