MCM6 indicates adverse tumor features and poor outcomes and promotes G1/S cell cycle progression in neuroblastoma

Yaoyao Gu,Yeming Wu,Xiaoxiao Hu,Kai Chen,Cheng Cheng,Zhixiang Wu,Xiaowei Liu

doi:10.1186/s12885-021-08344-z

Abstract

BackgroundMinichromosome maintenance complex component 6 (MCM6), as an important replication permission factor, is involved in the pathogenesis of various tumors. Here we studied the expression of MCM6 in neuroblastoma and its influence on tumor characteristics and prognosis.MethodsPublicly available datasets were used to explore the influence of the differential expression of MCM6 on neuroblastoma tumor stage, risk and prognosis. In cell experiments, human neuroblastoma cell lines SK-N-SH and SK-N-BE [ (2)] were utilized to verify the ability of MCM6 to promote cell proliferation, migration and invasion. We further explored the possible molecular mechanism of MCM6 affecting the phenotype of neuroblastoma cells by mutual verification of RNA-seq and western blotting, and flow cytometry to inquire about its potential specific roles in the cell cycle.ResultsThrough multiple datasets mining, we found that high expression of MCM6 was positively correlated with elevated tumor stage, high risk and poor prognosis in neuroblastoma. At the cellular level, neuroblastoma cell proliferation, migration and invasion were significantly inhibited after MCM6 was interfered by siRNA. Mutual verification of RNA-seq and western blotting suggested that the downstream cell cycle-related genes were differentially expressed after MCM6 interference. Flow cytometric analysis revealed that neuroblastoma cells were blocked in G1/S phase after MCM6 interference.ConclusionMCM6 is considered to be the driving force of G1/S cell cycle progression, and it is also a prognostic marker and a potential novel therapeutic target in neuroblastoma.

Highlights

Minichromosome maintenance complex component 6 (MCM6), as an important replication permission factor, is involved in the pathogenesis of various tumors
We found in this cohort that high expression of MCM6 was positively correlated with worse histopathological typing (Table 1, twotailed Spearman’s correlation, r = 0.671, p < 0.0001)
We performed Western blotting on 28 cases of this batch of clinical samples to detect the expression level of MCM6 protein, and found that it was basically consistent with the expression of mRNA (Figure S1)

Summary

Introduction

Minichromosome maintenance complex component 6 (MCM6), as an important replication permission factor, is involved in the pathogenesis of various tumors. Neuroblastoma is the most common extracranial solid tumor in infants, with 25–50 cases per million individuals [1]. It originates from the sympathetic nervous system. Evidence has shown that MCM family proteins act as helicases in the initial stage of DNA replication and are key regulators of cell cycle checkpoints [7]. The binding of MCM6 to Cdt, another component of the pre-replication complex, is the key to promoting the loading of the MCM complex on the chromatin for replication permission [9], so it is a potential marker for tumor diagnosis and treatment

Methods

Results

Discussion

Conclusion