Ablation of MCM10 using CRISPR/Cas9 restrains the growth and migration of esophageal squamous cell carcinoma cells through inhibition of Akt signaling
Authors Yan J, Du P, Jia Y, Chang Z, Gan S, Xu X, Wang Y, Qin Y, Kan Q
Received 14 November 2017
Accepted for publication 11 April 2018
Published 6 June 2018 Volume 2018:11 Pages 3323—3333
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Ingrid Espinoza
1Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 3National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou, China; 4Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 5Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Introduction: Minichromosome maintenance 10 (MCM10) is deregulated in several malignancies including cervical cancer and urothelial carcinoma. However, the expression and biologic role of MCM10 in esophageal squamous cell carcinoma (ESCC) is still unknown.
Methods: In this study, we performed immunohistochemistry and real-time polymerase chain reaction (PCR) analysis to examine the expression of MCM10 in ESCC and adjacent normal esophageal tissues. The associations of MCM10 expression with clinicopathologic parameters of ESCC were analyzed. Ablation of MCM10 through the CRISPR/Cas9 technology was conducted and its impact on ESCC cell growth and migration was investigated.
Results: The mRNA and protein expression levels of MCM10 were significantly greater in ESCC than in normal tissues (P<0.001). The expression of MCM10 was significantly associated with age at diagnosis (P=0.033), but not with gender, differentiation grade, invasion status, or tumor–node–metastasis (TNM) stage. Knockout of MCM10 significantly suppressed the proliferation, colony formation, and migration capacity of EC109 ESCC cells, compared to control cells harboring wild-type MCM10. Mechanistically, MCM10 depletion markedly reduced the phosphorylation of Akt. Overexpression of constitutively active Akt significantly restored the aggressive phenotype of MCM10-null EC109 cells.
Conclusion: In conclusion, these results suggest that MCM10 acts as an oncogene in ESCC through activation of Akt signaling and represents a promising therapeutic target for this malignancy.
Keywords: esophageal cancer, growth, migration, minichromosome maintenance proteins
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